Exon Junction Complex Research Articles

Mapping multiple RNA modifications simultaneously by proximity barcode sequencing.

RNA is subject to a multitude of different chemical modifications that collectively represent the epitranscriptome. Individual RNA modifications including N6-methyladenosine (m 6 A) on mRNA play essential roles in the posttranscriptional control of gene expression. Recent technological advances have enabled the transcriptome-wide mapping of certain RNA modifications, to reveal their broad relevance and characteristic distribution patterns. However, convenient methods that enable the simultaneous mapping of multiple different RNA marks within the same sample are generally lacking. Here we present EpiPlex RNA modification profiling, a bead-based proximity barcoding assay with sequencing readout that expands the scope of molecular recognition-based RNA modification detection to multiple targets, while providing relative quantification and enabling low RNA input. Measuring signal intensity against spike-in controls provides relative quantification, indicative of the RNA mod abundance at each locus. We report on changes in the modification status of HEK293T cells upon treatment with pharmacological inhibitors separately targeting METTL3, the dominant m 6 A writer enzyme, and the EIF4A3 component of the exon junction complex (EJC). The treatments resulted in decreased or increased m 6 A levels, respectively, without effect on inosine levels. Inhibiting the helicase activity of EIF4A3 and EIF4A3 knockdown both cause a significant increase of m 6 A sites near exon junctions, consistent with the previously reported role of EIF4A3 in shaping the m 6 A landscape. Thus, EpiPlex offers a reliable and convenient method for simultaneous mapping of multiple RNA modifications to facilitate epitranscriptome studies.

The oncogenic role of EIF4A3/CDC20 axis in the endometrial cancer.

Eukaryotic initiation factor 4A-3 (EIF4A3) is a key component of the exon junction complex (EJC) and is extensively involved in RNA splicing, inducing mRNA decay, and regulating the cell cycle and apoptosis. However, the potential role of EIF4A3 in EC has not been comprehensively investigated and remains unknown. Here, we report that the expression level of EIF4A3 is dramatically elevated in endometrial cancer (EC) samples compared with normal EC samples via bioinformatics analysis and immunohistochemistry analysis, and that high expression of EIF4A3 promotes the proliferation, migration, and invasion of EC cells. Mechanistically, we found that high EIF4A3 expression stabilized cell division cyclin 20 (CDC20) mRNA, and high EIF4A3 expression induced pro-carcinogenic effects in EC cells that were efficiently antagonized upon knockdown of CDC20, as well as Apcin, an inhibitor of CDC20. These findings reveal a novel mechanism by which high expression of EIF4A3 induces CDC20 upregulation, thus leading to EC tumorigenesis and metastasis, indicating a potential treatment strategy for EC patients with high EIF4A3 expression using Apcin. KEY MESSAGES: The expression level of EIF4A3 was dramatically elevated in endometrial cancer (EC) samples compared with normal endometrial cancer samples. High EIF4A3 expression stabilized CDC20 mRNA, and high EIF4A3 expression induced pro-carcinogenic effect in EC cells which was efficiently antagonized upon knockdown of CDC20. Apcin, an inhibitor of CDC20, could effectively counteract high expression of EIF4A3 inducing EC tumourigenesis and metastasis, indicating the potential treatment strategy for EC patients with EIF4A3 high expression by using Apcin.

Nonsense-Mediated mRNA Decay in Human Health and Diseases: Current Understanding, Regulatory Mechanisms and Future Perspectives.

Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism that is conserved across all eukaryotes ensuring the quality of transcripts by targeting messenger RNA (mRNA) harbouring premature stop codons. It regulates the gene expression by targeting aberrant mRNA carrying pre-termination codons (PTCs) and eliminates C-terminal truncated proteins. NMD distinguishes aberrant and non-aberrant transcript by looking after long 3' UTRs and exon-junction complex (EJC) downstream of stop codon that indicate the presence of PTC. Therefore, NMD modulates cellular surveillance and eliminates the truncated proteins but if the PTC escapes the surveillance pathway it can lead to potential negative phenotype resulting in genetic diseases. The alternative splicing also contributes in formation of NMD-sensitive isoforms by introducing PTC. NMD plays a complex role in cancer, it can either aggravate or downregulates the tumour. Some tumours agitate NMD to deteriorate mRNAs encoding tumour suppressor proteins, stress response proteins and neoantigens. In other case, tumours suppress the NMD to encourage the expression of oncoproteins for tumour growth and survival. This mechanism augmented in the development of new therapeutics by PTC read-through mechanism and personalized medicine. Detailed studies on NMD surveillance will possibly lead towards development of strategies for improving human health aligning with United Nations sustainable development goals (SDG 3: Good health and well-being). The potential therapeutic applications of NMD pose a challenge in terms of safe and effective modulation. Understanding the complexities of NMD regulation and its interaction with other cellular processes can lead to the development of new interventions for various diseases.

Paramyxovirus matrix proteins modulate host cell translation via exon-junction complex interactions in the cytoplasm.

Viruses have evolved myriad strategies to exploit the translation machinery of host cells to potentiate their replication. However, how paramyxovirus (PMVs) modulate cellular translation for their own benefit has not been systematically examined. Utilizing puromycylation labeling, overexpression of individual viral genes, and infection with wild-type virus versus its gene-deleted counterpart, we found that PMVs significantly inhibit host cells' nascent peptide synthesis during infection, with the viral matrix being the primary contributor to this effect. Using the rNiV-NPL replicon system, we discovered that the viral matrix enhances viral protein translation without affecting viral mRNA transcription and suppresses host protein expression at the translational level. Polysome profile analysis revealed that the HPIV3 matrix promotes the association of viral mRNAs with ribosomes, thereby enhancing their translation efficiency during infection. Intriguingly, our NiV-Matrix interactome identified the core exon-junction complex (cEJC), critical for mRNA biogenesis, as a significant component that interacts with the paramyxoviral matrix predominantly in the cytoplasm. siRNA knockdown of eIF4AIII simulated the restriction of cellular functions by the viral matrix, leading to enhanced viral gene translation and a reduction in host protein synthesis. Moreover, siRNA depletion of cEJC resulted in a 2-3 log enhancement in infectious virus titer for various PMVs but not SARS-CoV-2, enterovirus D68, or influenza virus. Our findings characterize a host translational interference mechanism mediated by viral matrix and host cEJC interactions. We propose that the PMV matrix redirects ribosomes to translate viral mRNAs at the expense of host cell transcripts, enhancing viral replication, and thereby enhancing viral replication. These insights provide a deeper understanding of the molecular interactions between paramyxoviruses and host cells, highlighting potential targets for antiviral strategies.

Rice BARENTSZ genes are required to maintain floral developmental stability against temperature fluctuations.

BARENTSZ (BTZ), a core component of the exon junction complex, regulates diverse developmental processes in animals. However, its evolutionary and developmental roles in plants remain elusive. Here, we revealed that three groups of paralogous BTZ genes existed in Poaceae, and Group 2 underwent loss-of-function mutations during evolution. They showed surprisingly low (~33%) sequence identities, implying functional divergence. Two genes retained in rice, OsBTZ1 and OsBTZ3, were edited; however, the resultant osbtz1 and osbtz3 mutants showed similar floral morphological and functional defects at a low frequency. When growing under low-temperature conditions, developmental abnormalities became pronounced, and new floral variations were induced. In particular, stamen and carpel functionality was impaired in these rice btz mutants. The double-gene mutant osbtz1/3 shared these floral defects with an increased frequency, which was further induced under low-temperature conditions. OsBTZs interacted with OsMADS7 and OsMADS8, and the floral expressions of the OsTGA10 and MADS-box genes were correlatively altered in these osbtz mutants and responded to low-temperature treatment. These novel findings demonstrate that two highly diverged OsBTZs are required to maintain floral developmental stability under low-temperature conditions, and play an integral role in male and female fertility, thus providing new insights into the indispensable roles of BTZ genes in plant development and adaptive evolution.

The RNA-binding protein EIF4A3 promotes axon development by direct control of the cytoskeleton

The exon junction complex (EJC), nucleated by EIF4A3, is indispensable for mRNA fate and function throughout eukaryotes. We discover that EIF4A3 directly controls microtubules, independent of RNA, which is critical for neural wiring. While neuronal survival in the developing mouse cerebral cortex depends upon an intact EJC, axonal tract development requires only Eif4a3. Using human cortical organoids, we show that EIF4A3 disease mutations also impair neuronal growth, highlighting conserved functions relevant for neurodevelopmental pathology. Live imaging of growing neurons shows that EIF4A3 is essential for microtubule dynamics. Employing biochemistry and competition experiments, we demonstrate that EIF4A3 directly binds to microtubules, mutually exclusive of the EJC. Finally, invitro reconstitution assays and rescue experiments demonstrate that EIF4A3 is sufficient to promote microtubule polymerization and that EIF4A3-microtubule association is a major contributor to axon growth. This reveals a fundamental mechanism by which neurons re-utilize core gene expression machinery to directly control the cytoskeleton.

M6A demethylase OsALKBH5 is required for double-strand break formation and repair by affecting mRNA stability in rice meiosis.

N6-methyladenosine (m6A) RNA modification is the most prevalent messenger RNA (mRNA) modification in eukaryotes and plays critical roles in the regulation of gene expression. m6A is a reversible RNA modification that is deposited by methyltransferases (writers) and removed by demethylases (erasers). The function of m6A erasers in plants is highly diversified and their roles in cereal crops, especially in reproductive development essential for crop yield, are largely unknown. Here, we demonstrate that rice OsALKBH5 acts as an m6A demethylase required for the normal progression of male meiosis. OsALKBH5 is a nucleo-cytoplasmic protein, highly enriched in rice anthers during meiosis, that associates with P-bodies and exon junction complexes, suggesting that it is involved in regulating mRNA processing and abundance. Mutations of OsALKBH5 cause reduced double-strand break (DSB) formation, severe defects in DSB repair, and delayed meiotic progression, leading to complete male sterility. Transcriptome analysis and m6A profiling indicate that OsALKBH5-mediated m6A demethylation stabilizes the mRNA level of multiple meiotic genes directly or indirectly, including several genes that regulate DSB formation and repair. Our study reveals the indispensable role of m6A metabolism in post-transcriptional regulation of meiotic progression in rice.

Exon-junction complex association with stalled ribosomes and slow translation-independent disassembly

Exon junction complexes are deposited at exon-exon junctions during splicing. They are primarily known to activate non-sense mediated degradation of transcripts harbouring premature stop codons before the last intron. According to a popular model, exon-junction complexes accompany mRNAs to the cytoplasm where the first translating ribosome pushes them out. However, they are also removed by uncharacterized, translation-independent mechanisms. Little is known about kinetic and transcript specificity of these processes. Here we tag core subunits of exon-junction complexes with complementary split nanoluciferase fragments to obtain sensitive and quantitative assays for complex formation. Unexpectedly, exon-junction complexes form large stable mRNPs containing stalled ribosomes. Complex assembly and disassembly rates are determined after an arrest in transcription and/or translation. 85% of newly deposited exon-junction complexes are disassembled by a translation-dependent mechanism. However as this process is much faster than the translation-independent one, only 30% of the exon-junction complexes present in cells at steady state require translation for disassembly. Deep RNA sequencing shows a bias of exon-junction complex bound transcripts towards microtubule and centrosome coding ones and demonstrate that the lifetimes of exon-junction complexes are transcript-specific. This study provides a dynamic vision of exon-junction complexes and uncovers their unexpected stable association with ribosomes.

Human disease-causing mutations result in loss of leiomodin 2 through nonsense-mediated mRNA decay.

The leiomodin (Lmod) family of actin-binding proteins play a critical role in muscle function, highlighted by the fact that mutations in all three family members (LMOD1-3) result in human myopathies. Mutations in the cardiac predominant isoform, LMOD2 lead to severe neonatal dilated cardiomyopathy. Most of the disease-causing mutations in the LMOD gene family are nonsense, or frameshift, mutations predicted to result in expression of truncated proteins. However, in nearly all cases of disease, little to no LMOD protein is expressed. We show here that nonsense-mediated mRNA decay, a cellular mechanism which eliminates mRNAs with premature termination codons, underlies loss of mutant protein from two independent LMOD2 disease-causing mutations. Furthermore, we generated steric-blocking oligonucleotides that obstruct deposition of the exon junction complex, preventing nonsense-mediated mRNA decay of mutant LMOD2 transcripts, thereby restoring mutant protein expression. Our investigation lays the initial groundwork for potential therapeutic intervention in LMOD-linked myopathies.

Abstract PO5-04-10: Clinical and prognostic value of MLN51 (Metastatic lymph node gene 51)/CASC3 (Cancer susceptibility candidate gene 3) in clinical breast cancer, connection with nodal and hormonal receptor status

Abstract Introduction: Metastatic Lymph Node Gene 51 Protein (MLN51) also known as Cancer Susceptibility Candidate Gene 3 Protein (CASC3) or Barentsz (BTZ) is a molecule that was first identified in malignant breast tumours. The CASC3 gene encodes the protein that binds to mRNA and is a key component of the exon junction complex (EJC), playing an important role in the metabolism of mRNA and in cellular recovery after stress responses. It is not clear, however, if MLN51 has a clinical value in assessing the disease progression of breast cancer. Methods: We analysed the transcription expression levels of MLN51 in a cohort of human breast cancer tissues and correlated the expression pattern with clinical outcome, pathological type and hormonal receptor status. Results: High levels of MLN51 was found to be a favourable prognostic indicator for overall survival (p=0.008, Hazard Ratio [HR=0.262]), the prognostic value being independent of other clinical and pathological factors. Likewise, high levels of MLN51 were also a significant and independent predictive factor for disease free survival (DFS) (p=0.003, HR=0.262). It was found that the favourable prediction in both OS and DFS was associated with node positive tumours, with significance with OS (p=0.004), compared in node negative tumours (p=0.143) and to DFS (p=0.001 in node positive compared with p=0.079 in node negative tumours). Levels of MLN51 had a significant correlation with EGFR in both normal and tumour mammary tissues but correlated with Her-2 and Her-3 in tumour tissues only. The prognostic power of MLN51 for DFS was significant in both Her-2 positive and Her-2 negative (p=0.003 and p=0.012) tumours and in ER negative tumours (p=0.003). The prediction for OS by MLN51 was particularly strong for Her-2 positive and ER positive (p=0.007 for both) tumours. Conclusions: MLN51 (CASC3) is a favourable prognostic factor in patients with breast cancer. This is clearly linked to the nodal status and hormone receptor status, particularly ER and HER-2. Citation Format: Binbin Cong, Tracey Martin, Xiaoshan Cao, Robert E Mansel, Eleri Davies, Wen Jiang. Clinical and prognostic value of MLN51 (Metastatic lymph node gene 51)/CASC3 (Cancer susceptibility candidate gene 3) in clinical breast cancer, connection with nodal and hormonal receptor status [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-04-10.

The exon junction complex is required for DMD gene splicing fidelity and myogenic differentiation

Deposition of the exon junction complex (EJC) upstream of exon-exon junctions helps maintain transcriptome integrity by preventing spurious re-splicing events in already spliced mRNAs. Here we investigate the importance of EJC for the correct splicing of the 2.2-megabase-long human DMD pre-mRNA, which encodes dystrophin, an essential protein involved in cytoskeletal organization and cell signaling. Using targeted RNA-seq, we show that knock-down of the eIF4A3 and Y14 core components of EJC in a human muscle cell line causes an accumulation of mis-splicing events clustered towards the 3′ end of the DMD transcript (Dp427m). This deregulation is conserved in the short Dp71 isoform expressed ubiquitously except in adult skeletal muscle and is rescued with wild-type eIF4A3 and Y14 proteins but not with an EJC assembly-defective mutant eIF4A3. MLN51 protein and EJC-associated ASAP/PSAP complexes independently modulate the inclusion of the regulated exons 71 and 78. Our data confirm the protective role of EJC in maintaining splicing fidelity, which in the DMD gene is necessary to preserve the function of the critical C-terminal protein–protein interaction domain of dystrophin present in all tissue-specific isoforms. Given the role of the EJC in maintaining the integrity of dystrophin, we asked whether the EJC could also be involved in the regulation of a mechanism as complex as skeletal muscle differentiation. We found that eIF4A3 knockdown impairs myogenic differentiation by blocking myotube formation. Collectively, our data provide new insights into the functional roles of EJC in human skeletal muscle.

The Exon Junction Complex Factor RBM8A in Glial Fibrillary Acid Protein-Expressing Astrocytes Modulates Locomotion Behaviors.

The role of RNA Binding Motif Protein 8a (RBM8A), an exon junction complex (EJC) component, in neurodevelopmental disorders has been increasingly studied for its crucial role in regulating multiple levels of gene expression. It regulates mRNA splicing, translation, and mRNA degradation and influences embryonic development. RBM8A protein is expressed in both neurons and astrocytes, but little is known about RBM8A's specific role in glial fibrillary acid protein (GFAP)-positive astrocytes. To address the role of RBM8A in astrocytes, we generated a conditional heterozygous knockout (KO) mouse line of Rbm8a in astrocytes using a GFAP-cre line. We confirmed a decreased expression of RBM8A in astrocytes of heterozygous conditional KO mice via RT-PCR and Sanger sequencing, as well as qRT-PCR, immunohistochemistry, and Western blot. Interestingly, these mice exhibit significantly increased movement and mobility, alongside sex-specific altered anxiety in the open field test (OFT) and elevated plus maze (OPM) tests. These tests, along with the rotarod test, suggest that these mice have normal motor coordination but hyperactive phenotypes. In addition, the haploinsufficiency of Rbm8a in astrocytes leads to a sex-specific change in astrocyte density in the dentate gyrus. This study further reveals the contribution of Rbm8a deletion to CNS pathology, generating more insights via the glial lens of an Rbm8a model of neurodevelopmental disorder.

A system of reporters for comparative investigation of EJC-independent and EJC-enhanced nonsense-mediated mRNA decay.

Nonsense-mediated mRNA decay (NMD) is a network of pathways that degrades transcripts that undergo premature translation termination. In mammals, NMD can be divided into the exon junction complex (EJC)-enhanced and EJC-independent branches. Fluorescence- and luminescence-based reporters have long been effective tools to investigate NMD, yet existing reporters largely focus on the EJC-enhanced pathway. Here, we present a system of reporters for comparative studies of EJC-independent and EJC-enhanced NMD. This system also enables the study of NMD-associated outcomes such as premature termination codon (PTC) readthrough and truncated protein degradation. These reporters are compatible with fluorescence or luminescence-based readouts via transient transfection or stable integration. Using this reporter system, we show that EJC-enhanced NMD RNA levels are reduced by 2- or 9-fold and protein levels are reduced by 7- or 12-fold compared to EJC-independent NMD, depending on the reporter gene used. Additionally, the extent of readthrough induced by G418 and an NMD inhibitor (SMG1i), alone and in combination, varies across NMD substrates. When combined, G418 and SMG1i increase readthrough product levels in an additive manner for EJC-independent reporters, while EJC-enhanced reporters show a synergistic effect. We present these reporters as a valuable toolkit to deepen our understanding of NMD and its associated mechanisms.

The exon-junction complex helicase eIF4A3 holds therapeutic potential in acute myeloid leukemia

The exon-junction complex helicase eIF4A3 holds therapeutic potential in acute myeloid leukemia

Comprehensive mapping of exon junction complex binding sites reveals universal EJC deposition in Drosophila

BackgroundThe exon junction complex (EJC) is involved in most steps of the mRNA life cycle, ranging from splicing to nonsense-mediated mRNA decay (NMD). It is assembled by the splicing machinery onto mRNA in a sequence-independent manner. A fundamental open question is whether the EJC is deposited onto all exon‒exon junctions or only on a subset of them. Several previous studies have made observations supportive of the latter, yet these have been limited by methodological constraints.ResultsIn this study, we sought to overcome these limitations via the integration of two different approaches for transcriptome-wide mapping of EJCs. Our results revealed that nearly all, if not all, internal exons consistently harbor an EJC in Drosophila, demonstrating that EJC presence is an inherent consequence of the splicing reaction. Furthermore, our study underscores the limitations of eCLIP methods in fully elucidating the landscape of RBP binding sites. Our findings highlight how highly specific (low false positive) methodologies can lead to erroneous interpretations due to partial sensitivity (high false negatives).ConclusionsThis study contributes to our understanding of EJC deposition and its association with pre-mRNA splicing. The universal presence of EJC on internal exons underscores its significance in ensuring proper mRNA processing. Additionally, our observations highlight the need to consider both specificity and sensitivity in RBP mapping methodologies.

An interaction between eIF4A3 and eIF3g drives the internal initiation of translation.

An RNA structure or modified RNA sequences can provide a platform for ribosome loading and internal translation initiation. The functional significance of internal translation has recently been highlighted by the discovery that a subset of circular RNAs (circRNAs) is internally translated. However, the molecular mechanisms underlying the internal initiation of translation in circRNAs remain unclear. Here, we identify eIF3g (a subunit of eIF3 complex) as a binding partner of eIF4A3, a core component of the exon-junction complex (EJC) that is deposited onto spliced mRNAs and plays multiple roles in the regulation of gene expression. The direct interaction between eIF4A3-eIF3g serves as a molecular linker between the eIF4A3 and eIF3 complex, thereby facilitating internal ribosomal entry. Protein synthesis from in vitro-synthesized circRNA demonstrates eIF4A3-driven internal translation, which relies on the eIF4A3-eIF3g interaction. Furthermore, our transcriptome-wide analysis shows that efficient polysomal association of endogenous circRNAs requires eIF4A3. Notably, a subset of endogenous circRNAs can express a full-length intact protein, such as β-catenin, in an eIF4A3-dependent manner. Collectively, our results expand the understanding of the protein-coding potential of the human transcriptome, including circRNAs.

Identification and bioinformatics analysis of a novel mutation in PLA2G6 gene in a patient with neurodegenerative disorder

PLA2G6-associated neurodegeneration disorders are a group of conditions that result from mutations in the PLA2G6 gene. These disorders can cause a range of symptoms affecting the brain and nervous system, such as movement problems, cognitive decline, and vision loss. In this case, Whole Exome Sequencing (WES) was conducted on a 9-year-old boy born to consanguineous parents, who have an increased risk of passing on recessive genetic disorders. Although the boy did not exhibit any clinical symptoms until he was seven months old, his condition deteriorated severely by the age of two, rendering him unable to sit or move around, and he did not develop the ability to speak. DNAs were extracted from the blood samples of the proband (the 9-year-old boy) and his parents. The proband's DNA was sequenced using WES to identify potential disease-causing mutations. To confirm the WES findings, PCR-Sanger sequencing analysis was performed on the DNAs obtained from the proband (the 9-year-old boy) and his parents. The effect of the mutation on the protein structure was studied using the I-TASSER web-tool, which uses computational methods to predict protein structure and function based on amino acid sequences.The analysis of WES data revealed a homozygous dinucleotide TG insertion at position c.1362–1363 in exon 10 of the PLA2G6 gene (NC_000022.11(NM_003560.4):c.1362_1363insTG). This insertion introduced a premature stop codon at position 455 (p.Met455Ter) in the protein sequence. The validation of the WES results using PCR-Sanger sequencing confirmed the presence of the mutation in the proband and revealed that both parents were carriers of the mutation. The premature stop codon, located 65 nucleotides before the exon-junction complex, is likely to be detected by the nonsense-mediated mRNA decay (NMD) pathway, leading to the degradation of the mRNA. The use of the I-TASSER web-tool further supported the findings by demonstrating significant structural and functional changes in the mutant protein. Observing a very severe phenotype in our case supports the idea that the mutation was highly deleterious.

Localization of oskar mRNA by agglomeration in ribonucleoprotein granules.

Localization of oskar mRNA to the posterior of the Drosophila oocyte is essential for abdominal patterning and germline development. oskar localization is a multi-step process involving temporally and mechanistically distinct transport modes. Numerous cis-acting elements and trans-acting factors have been identified that mediate earlier motor-dependent transport steps leading to an initial accumulation of oskar at the posterior. Little is known, however, about the requirements for the later localization phase, which depends on cytoplasmic flows and results in the accumulation of large oskar ribonucleoprotein granules, called founder granules, by the end of oogenesis. Using super-resolution microscopy, we show that founder granules are agglomerates of smaller oskar transport particles. In contrast to the earlier kinesin-dependent oskar transport, late-phase localization depends on the sequence as well as on the structure of the spliced oskar localization element (SOLE), but not on the adjacent exon junction complex deposition. Late-phase localization also requires the oskar 3' untranslated region (3' UTR), which targets oskar to founder granules. Together, our results show that 3' UTR-mediated targeting together with SOLE-dependent agglomeration leads to accumulation of oskar in large founder granules at the posterior of the oocyte during late stages of oogenesis. In light of previous work showing that oskar transport particles are solid-like condensates, our findings indicate that founder granules form by a process distinct from that of well-characterized ribonucleoprotein granules like germ granules, P bodies, and stress granules. Additionally, they illustrate how an individual mRNA can be adapted to exploit different localization mechanisms depending on the cellular context.

First person – Nioosha Nekooie Marnany

ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Nioosha Nekooie Marnany is first author on ‘ Glucose oxidation drives trunk neural crest cell development and fate’, published in JCS. Nioosha conducted the research described in this article while a PhD student in Dr Sylvie Dufour and Dr Jean-Loup Duband's lab at Institut Mondor de Recherches Biomédicales, Université Paris-Est Créteil, France. Currently, she is a postdoc in the ‘Institut de Biologie, Ecole Normale Supérieure (IBENS)' in Paris, at Hervé Le Hire's lab where she is working on the relationship between the exon junction complex (EJC) and metabolism.

Exon Junction Complex Mediates the Cap-Independent Translation of Circular RNA.

EJC-mediated cap-independent translation of circRNA is implicated in the tumorigenesis of colorectal cancer.