High Translational Efficiency Research Articles

Comprehensive Analysis of Codon Usage Bias in Human Papillomavirus Type 51.

Human papillomavirus type 51 (HPV-51) is associated with various cancers, including cervical cancer. Examining the codon usage bias of the organism can offer valuable insights into its evolutionary patterns and its relationship with the host. This study comprehensively analyzed codon usage bias in HPV-51 by examining 64 complete genome sequences sourced from the NCBI GenBank database. Our analysis revealed no noteworthy preference for codon usage in HPV-51 overall. However, there was a noticeable bias towards A/T-ending codons, accompanied by GC3s below 32%. Dinucleotide frequency analysis revealed reduced frequencies for ApA, CpG, and TpC dinucleotides, while CpA and TpG dinucleotides were more frequent than others. Relative Synonymous Codon Usage analysis revealed 30 favored codons, primarily concluding with A/T nucleotides. Further analysis using Parity Rule 2, Effective Number of Codons plot, and neutrality plot indicated a balance between mutational pressure and natural selection, with natural selection being the primary force shaping codon usage bias. The Isoacceptor tRNA Pool analysis indicates that HPV-51 has a higher translation efficiency within the human cellular translational system. Moreover, the Codon Adaptation Index and Relative Codon Deoptimization Index analyses suggested a moderate adaptation of HPV-51 to human codon preferences. Our discoveries offer valuable perspectives on how HPV-51 evolves and uses genetic codes, contributing to a deeper comprehension of its endurance and disease-causing potential.

Prediction of the effects of the top 10 synonymous mutations from 26645 SARS-CoV-2 genomes of early pandemic phase

Background The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had led to a global pandemic since December 2019. SARS-CoV-2 is a single-stranded RNA virus, which mutates at a higher rate. Multiple works had been done to study nonsynonymous mutations, which change protein sequences. However, there is little study on the effects of SARS-CoV-2 synonymous mutations, which may affect viral fitness. This study aims to predict the effect of synonymous mutations on the SARS-CoV-2 genome. Methods A total of 26645 SARS-CoV-2 genomic sequences retrieved from Global Initiative on Sharing all Influenza Data (GISAID) database were aligned using MAFFT. Then, the mutations and their respective frequency were identified. Multiple RNA secondary structures prediction tools, namely RNAfold, IPknot++ and MXfold2 were applied to predict the effect of the mutations on RNA secondary structure and their base pair probabilities was estimated using MutaRNA. Relative synonymous codon usage (RSCU) analysis was also performed to measure the codon usage bias (CUB) of SARS-CoV-2. Results A total of 150 synonymous mutations were identified. The synonymous mutation identified with the highest frequency is C3037U mutation in the nsp3 of ORF1a. Of these top 10 highest frequency synonymous mutations, C913U, C3037U, U16176C and C18877U mutants show pronounced changes between wild type and mutant in all 3 RNA secondary structure prediction tools, suggesting these mutations may have some biological impact on viral fitness. These four mutations show changes in base pair probabilities. All mutations except U16176C change the codon to a more preferred codon, which may result in higher translation efficiency. Conclusion Synonymous mutations in SARS-CoV-2 genome may affect RNA secondary structure, changing base pair probabilities and possibly resulting in a higher translation rate. However, lab experiments are required to validate the results obtained from prediction analysis.

199 Awardee Talk: Insights into translational regulation through tRNA sequencing, RNA sequencing, and ribosome profiling

Abstract Translation acts as an additional layer of regulation that has an important role in gene expression and function. Due to a phenomenon called codon usage bias, highly expressed genes are thought to be codon-biased to support efficient translation. As more than one codon can code for the same amino acid (synonymous codons), organisms may exhibit preferences for specific codons that facilitate increased expression of important genes due to variations in the availability of corresponding tRNAs. Advances in sequencing technologies have recently permitted the study of the translatome, which refers to the entire population of mRNA associated with ribosomes for protein synthesis and can be investigated through ribosome profiling. This cutting-edge technique allows the identification of actively translated regions, but can also reveal translational pausing events that stem from the presence of SNPs. Our previous research has demonstrated variation in tRNA expression across tissues and different states of health, leading us to consider the connection between tRNA abundance and translational stalling due to SNPs. By coupling ribosome profiling with tRNA sequencing and RNA sequencing, we have investigated all elements of translational machinery to predict translational efficiency, estimate proteome composition, and evaluate tRNA abundance as a source of genetic variation. In this work, we utilized ribosome profiling, tRNAseq, and RNAseq and performed an integrative analysis in bovine tissues (kidney, liver and muscle) as well as murine myoblast cell lines (C2C12). By applying these methods to different bovine tissues, we were able to explore the interplay between tRNA availability and translational stalling events. Moreover, we have identified translationally regulated genes underlying tissue-specific biological processes and found that many upregulated and downregulated genes coincided with high and low translational efficiency respectively. We have also successfully defined stalling sites that depict the regulatory information encoded within the coding sequence of transcripts, which could control translation rate and facilitate proper protein folding. Through the implementation of these next generation sequencing (NGS) methods to cell culture, we were able to evaluate the translatome at various time points (0-min, 30-min, 60-min, and 4-h) post-induction of differentiation. Where most studies have focused on molecular changes between differentiating myoblasts and multinucleated myotubes that are present 7 d after differentiation, we focus on the earliest stages of muscle differentiation that initiate muscle development and therefore kickstart the process of meat production. This work offers an atlas of distinctive stalling sites across bovine tissues and various stages of muscle differentiation, which provides an opportunity to predict codon optimality and understand tissue-specific or time-specific mechanisms of regulating protein synthesis.

Discovery of high-expressing lncRNA-derived sORFs as potential tumor-associated antigens in hepatocellular carcinoma.

This study is based on deep mining of Ribo-seq data for the identification of lncRNAs that have highly expressed sORFs in HCC. In this paper, dynamic prospects associated with sORFs acting as newly defined tumor-specific epitopes are discussed with possible improvement in strategies for tumor immunotherapy. Using ribosome profiling to identify and characterize sORFs within lncRNAs in HCC, identify potential therapeutic targets and tumor-specific epitopes applicable for immunotherapy. MetamORF performed the identification of sORFs with deep analysis of the data of ribosome profiling in lncRNAs associated with HCC. The translation efficiency in these molecules was estimated, and epitope prediction was done by pVACbind. Peptide search was done to check the presence of micropeptides translated from these identified sORFs. validated translational activity and identified potential epitopes. Higher translation efficiency was noted in the case of lncRNAs associated with HCC compared to normal tissues. Of particular note is ORF3418981, which results in the highest expression and has supporting experimental evidence at the protein level. Epitope prediction identified a putative epitope at the C-terminus of ORF3418981. This study uncovers the as-yet-unknown potential of lncRNA-derived sORFs as sources of tumor antigens, shifting the research focus from protein-coding genes to non-coding RNAs also in the HCC context. Moreover, this study highlights the contribution of a subset of lncRNAs, especially LINC00152, to the development of tumors and modulation of the immune response by its sORFs.

METTL14 promotes lipid metabolism reprogramming and sustains nasopharyngeal carcinoma progression via enhancing m6A modification of ANKRD22 mRNA.

N6-methyladenosine (m6A) modification is essential for modulating RNA processing as well as expression, particularly in the context of malignant tumour progression. However, the exploration of m6A modification in nasopharyngeal carcinoma (NPC) remains very limited. RNA m6A levels were analysed in NPC using m6A dot blot assay. The expression level of methyltransferase-like 14 (METTL14) within NPC tissues was analysed from public databases as well as RT-qPCR and immunohistochemistry. The influences on METTL14 expression on NPC proliferation and metastasis were explored via in vitro as well as in vivo functional assays. Targeted genes of METTL14 were screened using the m6A and gene expression profiling microarray data. Actinomycin D treatment and polysome analysis were used to detect the half-life and translational efficiency of ANKRD22. Flow cytometry, immunofluorescence and immunoprecipitation were used to validate the role of ANKRD22 on lipid metabolism in NPC cells. ChIP-qPCR analysis of H3K27AC signalling near the promoters of METTL14, GINS3, POLE2, PLEK2 and FERMT1 genes. We revealed METTL14, in NPC, correlating with poor patient prognosis. In vitro and in vivo assays indicated METTL14 actively promoted NPC cells proliferation and metastasis. METTL14 catalysed m6A modification on ANKRD22 messenger ribonucleic acid (mRNA), recognized by the reader IGF2BP2, leading to increased mRNA stability and higher translational efficiency. Moreover, ANKRD22, a metabolism-related protein on mitochondria, interacted with SLC25A1 to enhance citrate transport, elevating intracellular acetyl-CoA content. This dual impact of ANKRD22 promoted lipid metabolism reprogramming and cellular lipid synthesis while upregulating the expression of genes associated with the cell cycle (GINS3 and POLE2) and the cytoskeleton (PLEK2 and FERMT1) through heightened epigenetic histone acetylation levels in the nucleus. Intriguingly, our findings highlighted elevated ANKRD22-mediated histone H3 lysine 27 acetylation (H3K27AC) signals near the METTL14 promoter, which contributes to a positive feedback loop perpetuating malignant progression in NPC. The identified METTL14-ANKRD22-SLC25A1 axis emerges as a promising therapeutic target for NPC, and also these molecules may serve as novel diagnostic biomarkers.

Importance of the ECM-receptor interaction for adaptive response to hypoxia based on integrated transcription and translation analysis.

Low dissolved oxygen (LO) conditions represent a major environmental challenge to marine life, especially benthic animals. For these organisms, drastic declines in oxygen availability (hypoxic events) can trigger mass mortality events and thus, act as agents of selection influencing the evolution of adaptations. In sea cucumbers, one of the most successful groups of benthic invertebrates, the exposure to hypoxic conditions triggers adaptive adjustments in metabolic rates and behaviour. It is unclear, however, how these adaptive responses are regulated and the genetic mechanisms underpinning them. Here, we addressed this knowledge gap by assessing the genetic regulation (transcription and translation) of hypoxia exposure in the sea cucumber Apostichopus japonicus. Transcriptional and translational gene expression profiles under short- and long-term exposure to low oxygen conditions are tightly associated with extracellular matrix (ECM)-receptor interaction in which laminin and collagen likely have important functions. Finding revealed that genes with a high translational efficiency (TE) had a relatively short upstream open reading frame (uORF) and a high uORF normalized minimal free energy, suggesting that sea cucumbers may respond to hypoxic stress via altered TE. These results provide valuable insights into the regulatory mechanisms that confer adaptive capacity to holothurians to survive oxygen deficiency conditions and may also be used to inform the development of strategies for mitigating the harmful effects of hypoxia on other marine invertebrates facing similar challenges.

Prediction of the effects of the top 10 synonymous mutations from 26645 SARS-CoV-2 genomes of early pandemic phase.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had led to a global pandemic since December 2019. SARS-CoV-2 is a single-stranded RNA virus, which mutates at a higher rate. Multiple works had been done to study nonsynonymous mutations, which change protein sequences. However, there is little study on the effects of SARS-CoV-2 synonymous mutations, which may affect viral fitness. This study aims to predict the effect of synonymous mutations on the SARS-CoV-2 genome. A total of 26645 SARS-CoV-2 genomic sequences retrieved from Global Initiative on Sharing all Influenza Data (GISAID) database were aligned using MAFFT. Then, the mutations and their respective frequency were identified. Multiple RNA secondary structures prediction tools, namely RNAfold, IPknot++ and MXfold2 were applied to predict the effect of the mutations on RNA secondary structure and their base pair probabilities was estimated using MutaRNA. Relative synonymous codon usage (RSCU) analysis was also performed to measure the codon usage bias (CUB) of SARS-CoV-2. A total of 150 synonymous mutations were identified. The synonymous mutation identified with the highest frequency is C3037U mutation in the nsp3 of ORF1a. Of these top 10 highest frequency synonymous mutations, C913U, C3037U, U16176C and C18877U mutants show pronounced changes between wild type and mutant in all 3 RNA secondary structure prediction tools, suggesting these mutations may have some biological impact on viral fitness. These four mutations show changes in base pair probabilities. All mutations except U16176C change the codon to a more preferred codon, which may result in higher translation efficiency. Synonymous mutations in SARS-CoV-2 genome may affect RNA secondary structure, changing base pair probabilities and possibly resulting in a higher translation rate. However, lab experiments are required to validate the results obtained from prediction analysis.

Inhibition of OCT4 binding at the MYCN locus induces neuroblastoma cell death accompanied by downregulation of transcripts with high-open reading frame dominance.

Amplification of MYCN is observed in high-risk neuroblastomas (NBs) and is associated with a poor prognosis. MYCN expression is directly regulated by multiple transcription factors, including OCT4, MYCN, CTCF, and p53 in NB. Our previous study showed that inhibition of p53 binding at the MYCN locus induces NB cell death. However, it remains unclear whether inhibition of alternative transcription factor induces NB cell death. In this study, we revealed that the inhibition of OCT4 binding at the MYCN locus, a critical site for the human-specific OCT4-MYCN positive feedback loop, induces caspase-2-mediated cell death in MYCN-amplified NB. We used the CRISPR/deactivated Cas9 (dCas9) technology to specifically inhibit transcription factors from binding to the MYCN locus in the MYCN-amplified NB cell lines CHP134 and IMR32. In both cell lines, the inhibition of OCT4 binding at the MYCN locus reduced MYCN expression, thereby suppressing MYCN-target genes. After inhibition of OCT4 binding, differentially downregulated transcripts were associated with high-open reading frame (ORF) dominance score, which is associated with the translation efficiency of transcripts. These transcripts were enriched in splicing factors, including MYCN-target genes such as HNRNPA1 and PTBP1. Furthermore, transcripts with a high-ORF dominance score were significantly associated with genes whose high expression is associated with a poor prognosis in NB. Because the ORF dominance score correlates with the translation efficiency of transcripts, our findings suggest that MYCN maintains the expression of transcripts with high translation efficiency, contributing to a poor prognosis in NB. In conclusion, the inhibition of OCT4 binding at the MYCN locus resulted in reduced MYCN activity, which in turn led to the downregulation of high-ORF dominance transcripts and subsequently induced caspase-2-mediated cell death in MYCN-amplified NB cells. Therefore, disruption of the OCT4 binding at the MYCN locus may serve as an effective therapeutic strategy for MYCN-amplified NB.

Untranslated Region Sequences and the Efficacy of mRNA Vaccines against Tuberculosis.

mRNA vaccines have been shown to be effective in combating the COVID-19 pandemic. The amount of research on the use of mRNAs as preventive and therapeutic modalities has undergone explosive growth in the last few years. Nonetheless, the issue of the stability of mRNA molecules and their translation efficiency remains incompletely resolved. These characteristics of mRNA directly affect the expression level of a desired protein. Regulatory elements of RNA-5' and 3' untranslated regions (UTRs)-are responsible for translation efficiency. An optimal combination of the regulatory sequences allows mRNA to significantly increase the target protein's expression. We assessed the translation efficiency of mRNA encoding of firefly luciferase with various 5' and 3'UTRs in vitro on cell lines DC2.4 and THP1. We found that mRNAs containing 5'UTR sequences from eukaryotic genes HBB, HSPA1A, Rabb, or H4C2, or from the adenoviral leader sequence TPL, resulted in higher levels of luciferase bioluminescence 4 h after transfection of DC2.4 cells as compared with 5'UTR sequences used in vaccines mRNA-1273 and BNT162b2 from Moderna and BioNTech. mRNA containing TPL as the 5'UTR also showed higher efficiency (as compared with the 5'UTR from Moderna) at generating a T-cell response in mice immunized with mRNA vaccines encoding a multiepitope antigen. By contrast, no effects of various 5'UTRs and 3'UTRs were detectable in THP1 cells, suggesting that the observed effects are cell type specific. Further analyses enabled us to identify potential cell type-specific RNA-binding proteins that differ in landing sites within mRNAs with various 5'UTRs and 3'UTRs. Taken together, our data indicate high translation efficiency of TPL as a 5'UTR, according to experiments on DC2.4 cells and C57BL/6 mice.

Cross-cultural English text translation strategy based on the Transformer model

Abstract The development of science and technology makes the cooperation and cultural exchanges between various countries more and more frequent. Machine translation has the advantages of high translation efficiency and low cost, and the research devoted to machine translation has become the current trend in the cross-cultural field. Based on the application form of cross-cultural perspective transformation in English text translation, this paper proposes cross-cultural text features using the Glove model and puts forward a neuro-machine translation strategy of optimizing the Transformer model with a multi-attention mechanism, which is used to solve the task of cross-cultural English text translation. In the Chinese translation task of cross-cultural English text, the translation accuracy of the model is negatively correlated with the sequence length. The average SER is 0.551, which has good anti-confusion performance. Furthermore, it appears to have a greater lexical richness and the number of idioms used when performing the translation task. Based on this study, the proposed English text translation technique achieves better results. It can replace manual translation to accomplish complex tasks and promote the development of translation cognition.

99 Noncoding Rnas Alter Our Interpretations of Genome to Phenome

Abstract Gene transcription and protein translation are core components in the process of gene expression. Previous research on the regulation of gene expression largely focuses on events prior to translation, including epigenetic regulation, transcription, and RNA processing. However, translation acts as an additional layer of regulation that plays an important role in gene expression and function. Highly expressed genes are thought to be codon-biased to support efficient translation, in which the encoded codons correspond to highly abundant tRNAs. Further, synonymous SNPs were once considered to be silent due to the degeneracy of the genetic code. However, synonymous SNPs may disturb protein abundance and function through alterations in translational efficiency and suboptimal pairing to lowly abundant tRNAs. Our previous study identified variation in tRNA expression within bovine liver and muscle tissue, suggesting tissue-specific modulation of translation. In addition, advances in sequencing technologies have recently permitted the study of the translatome, which refers to the entire population of mRNA associated with ribosomes for protein synthesis and can be investigated through ribosome profiling. Here, we applied Quantitative Mature tRNA sequencing (QuantM-tRNA-seq) and ribosome profiling to investigate the relationship between tRNA expression and translational stalling events. Moreover, we have identified translationally regulated genes underlying tissue-specific biological processes and found that many upregulated and downregulated genes coincided with high and low translational efficiency respectively. We have also successfully defined stalling sites that depict the regulatory information encoded within the coding sequence of transcripts, which could control translation rate and facilitate proper protein folding. This work offers an atlas of distinctive stalling sites across bovine tissues, which provides an opportunity to predict codon optimality and understand tissue-specific mechanisms of regulating protein synthesis.

Research progress in mRNA drug modification and its delivery system.

Messenger RNA (mRNA) has shown tremendous potential in disease prevention and therapy. The clinical application requires mRNA with enhanced stability and high translation efficiency, ensuring it not to be degraded by nuclease and to target to specific tissues and cells. The mRNA immunogenicity can be reduced by nucleotide modification, and its translation efficiency can be enhanced by codon optimization. The 5´ capping structure and 3´ poly A increase mRNA stability, and the addition of 5' and 3' non-translational region regulates mRNA translation initiation and protein production. A nanoparticle delivery system protects mRNA from degradation by ubiquitous nuclease, enhances its circulation concentration and assists it entrancing cytoplasm for the purpose of treatment and prevention. In this article, we review the recent advances of mRNA technology, discuss the methods and principles to enhance mRNA stability and translation efficiency; summarize the requirements involved in designing mRNA delivery systems with the potential of industrial translation and biomedical application. Furthermore, we provide insights into future directions of mRNA therapeutics to meet the need for personalized precision medicine.

Differential translation of mRNA isoforms underlies oncogenic activation of cell cycle kinase Aurora A

Aurora Kinase A (AURKA) is an oncogenic kinase with major roles in mitosis, but also exerts cell cycle- and kinase-independent functions linked to cancer. Therefore, control of its expression, as well as its activity, is crucial. A short and a long 3′UTR isoform exist for AURKA mRNA, resulting from alternative polyadenylation (APA). We initially observed that in triple-negative breast cancer, where AURKA is typically overexpressed, the short isoform is predominant and this correlates with faster relapse times of patients. The short isoform is characterized by higher translational efficiency since translation and decay rate of the long isoform are targeted by hsa-let-7a tumor-suppressor miRNA. Additionally, hsa-let-7a regulates the cell cycle periodicity of translation of the long isoform, whereas the short isoform is translated highly and constantly throughout interphase. Finally, disrupted production of the long isoform led to an increase in proliferation and migration rates of cells. In summary, we uncovered a new mechanism dependent on the cooperation between APA and miRNA targeting likely to be a route of oncogenic activation of human AURKA.

Differential translation of mRNA isoforms underlies oncogenic activation of cell cycle kinase Aurora A.

Aurora Kinase A (AURKA) is an oncogenic kinase with major roles in mitosis, but also exerts cell cycle- and kinase-independent functions linked to cancer. Therefore, control of its expression, as well as its activity, is crucial. A short and a long 3'UTR isoform exist for AURKA mRNA, resulting from alternative polyadenylation (APA). We initially observed that in triple-negative breast cancer, where AURKA is typically overexpressed, the short isoform is predominant and this correlates with faster relapse times of patients. The short isoform is characterized by higher translational efficiency since translation and decay rate of the long isoform are targeted by hsa-let-7a tumor-suppressor miRNA. Additionally, hsa-let-7a regulates the cell cycle periodicity of translation of the long isoform, whereas the short isoform is translated highly and constantly throughout interphase. Finally, disrupted production of the long isoform led to an increase in proliferation and migration rates of cells. In summary, we uncovered a new mechanism dependent on the cooperation between APA and miRNA targeting likely to be a route of oncogenic activation of human AURKA.

Integration of miRNA and mRNA analysis reveals the role of ribosome in to anti-artificial aging in sweetcorn

Sweetcorn is a kind of maize with high sugar content and has poor seed aging tolerance, which seriously limits its production. However, few studies have explored the artificial aging (AA) tolerance by miRNA-mRNA integration analysis in sweetcorn. Here, we characterized the physiological, biochemical and transcriptomic changes of two contrasting lines K62 and K107 treated with AA during time series. Both the germination indexes and antioxidant enzymes showed significant difference between two lines. The MDA content of AA-tolerant genotype K62 was significantly lower than that of K107 on the fourth and sixth day. Subsequently, 157 differentially expressed miRNAs (DEMIs) and 8878 differentially expressed mRNAs (DEMs) were identified by RNA-seq analysis under aging stress. The “ribosome” and “peroxisome” pathways were enriched to respond to aging stress, genes for both large units and small ribosomal subunits were significantly upregulated expressed and higher translation efficiency might exist in K62. Thirteen pairs of miRNA-target genes were obtained, and 8 miRNA-mRNA pairs might involve in ribosome protein and translation process. Our results elucidate the mechanism of sweetcorn response to AA at miRNA-mRNA level, and provide a new insight into sweetcorn AA response to stress.

Translational landscape in human early neural fate determination.

Gene expression regulation in eukaryotes is a multi-level process, including transcription, mRNA translation, and protein turnover. Many studies have reported the sophisticated transcriptional regulations during neural development, but the global translational dynamics are still ambiguous. Here, we differentiate human embryonic stem cells (ESCs) into neural progenitor cells (NPCs) with high efficiency and perform ribosome sequencing and RNA sequencing on both ESCs and NPCs. Data analysis reveals that translational controls engage in many critical pathways and contribute significantly to neural fate determination regulation. Furthermore, we show that the sequence characteristics in the untranslated region (UTR) might regulate translation efficiency. Specifically, genes with short 5'UTR and intense Kozak sequence are associated with high translation efficiency in human ESCs, while genes with long 3'UTR are related to high translation efficiency in NPCs. In addition, we have identified four biasedly-used codons (GAC, GAT, AGA, and AGG) and dozens of short open reading frames during neural progenitor differentiation. Thus, our study reveals the translational landscape during early human neural differentiation and provides insights into the regulation of cell fate determination at the translational level.

Integrated analysis of transcriptomic and proteomic data reveals novel regulators of soybean (Glycine max) hypocotyl development.

Hypocotyl elongation directly affects the seedling establishment and soil-breaking after germination. In soybean (Glycine max ), the molecular mechanisms regulating hypocotyl development remain largely elusive. To decipher the regulatory landscape, we conducted proteome and transcriptome analysis of soybean hypocotyl samples at different development stages. Our results showed that during hypocotyl development, many proteins were with extreme high translation efficiency (TE) and may act as regulators. These potential regulators include multiple peroxidases and cell wall reorganisation related enzymes. Peroxidases may produce ROS including H2 O2 . Interestingly, exogenous H2 O2 application promoted hypocotyl elongation, supporting peroxidases as regulators of hypocotyl development. However, a vast variety of proteins were shown to be with dramatically changed TE during hypocotyl development, including multiple phytochromes, plasma membrane intrinsic proteins (PIPs) and aspartic proteases. Their potential roles in hypocotyl development were confirmed by that ectopic expression of GmPHYA1 and GmPIP1-6 in Arabidopsis thaliana affected hypocotyl elongation. In addition, the promoters of these potential regulatory genes contain multiple light/gibberellin/auxin responsive elements, while the expression of some members in hypocotyls was significantly regulated by light and exogenous auxin/gibberellin. Overall, our results revealed multiple novel regulatory factors of soybean hypocotyl elongation. Further research on these regulators may lead to new approvals to improve soybean hypocotyl traits.

The Ribosome's Effect on Stem Cells and How Their Dysfunction Could Cause Cancer

Recently, the importance of ribosomes has greatly increased. It was discovered that they play a large role in the functionality of stem cells. This is due to the ribosome’s effect on translational efficiency. Without high translational efficiency, stem cells would lose the ability to differentiate into other cells. If stem cells become dysfunctional, whether it is due to malfunctioning ribosomes, lack of ribosomes, or other mutations, diseases could arise and tumors may form. In certain conditions, the tumor can be malignant and generate cancer. As more research is done on these connections, alternate treatments for cancer may be discovered and scientists may be able to figure out a way to prevent certain cancers from forming by starting at its molecular source. 

Prediction of the effects of the top 10 synonymous mutations from 26645 SARS-CoV-2 genomes

Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had led to a global pandemic since December 2019. SARS-CoV-2 is a single-stranded RNA virus, which mutates at a higher rate. Multiple works had been done to study nonsynonymous mutations, which change protein sequences. However, there is little study on the effects of SARS-CoV-2 synonymous mutations, which may affect viral fitness. This study aims to predict the effect of synonymous mutations on the SARS-CoV-2 genome. Methods: A total of 26645 SARS-CoV-2 genomic sequences retrieved from Global Initiative on Sharing all Influenza Data (GISAID) database were aligned using MAFFT. Then, the mutations and their respective frequency were identified. Multiple RNA secondary structures prediction tools, namely RNAfold, IPknot++ and MXfold2 were applied to predict the effect of the mutations on RNA secondary structure and their base pair probabilities was estimated using MutaRNA. Relative synonymous codon usage (RSCU) analysis was also performed to measure the codon usage bias (CUB) of SARS-CoV-2. Results: A total of 150 synonymous mutations were identified. The synonymous mutation identified with the highest frequency is C3037U mutation in the nsp3 of ORF1a.. Of these top 10 highest frequency synonymous mutations, C913U, C3037U, U16176C and C18877U mutants show pronounced changes between wild type and mutant in all 3 RNA secondary structure prediction tools, suggesting these mutations may have some biological impact on viral fitness. These four mutations show changes in base pair probabilities. All mutations except U16176C change the codon to a more preferred codon, which may result in higher translation efficiency. Conclusion: Synonymous mutations in SARS-CoV-2 genome may affect RNA secondary structure, changing base pair probabilities and possibly resulting in a higher translation rate. However, lab experiments are required to validate the results obtained from prediction analysis.

Nuclear and cytoplasmic poly(A) binding proteins (PABPs) favor distinct transcripts and isoforms.

The poly(A)-tail appended to the 3′-end of most eukaryotic transcripts plays a key role in their stability, nuclear transport, and translation. These roles are largely mediated by Poly(A) Binding Proteins (PABPs) that coat poly(A)-tails and interact with various proteins involved in the biogenesis and function of RNA. While it is well-established that the nuclear PABP (PABPN) binds newly synthesized poly(A)-tails and is replaced by the cytoplasmic PABP (PABPC) on transcripts exported to the cytoplasm, the distribution of transcripts for different genes or isoforms of the same gene on these PABPs has not been investigated on a genome-wide scale. Here, we analyzed the identity, splicing status, poly(A)-tail size, and translation status of RNAs co-immunoprecipitated with endogenous PABPN or PABPC in human cells. At steady state, many protein-coding and non-coding RNAs exhibit strong bias for association with PABPN or PABPC. While PABPN-enriched transcripts more often were incompletely spliced and harbored longer poly(A)-tails and PABPC-enriched RNAs had longer half-lives and higher translation efficiency, there are curious outliers. Overall, our study reveals the landscape of RNAs bound by PABPN and PABPC, providing new details that support and advance the current understanding of the roles these proteins play in poly(A)-tail synthesis, maintenance, and function.