Abstract
The identification of RNAs that are not translated into proteins was an important breakthrough, defining the diversity of molecules involved in eukaryotic regulation of gene expression. These non-coding RNAs can be divided into two main classes according to their length: short non-coding RNAs, such as microRNAs (miRNAs), and long non-coding RNAs (lncRNAs). The lncRNAs in association with other molecules can coordinate several physiological processes and their dysfunction may impact in several pathologies, including cancer and infectious diseases. They can control the flux of genetic information, such as chromosome structure modulation, transcription, splicing, messenger RNA (mRNA) stability, mRNA availability, and post-translational modifications. Long non-coding RNAs present interaction domains for DNA, mRNAs, miRNAs, and proteins, depending on both sequence and secondary structure. The advent of new generation sequencing has provided evidences of putative lncRNAs existence; however, the analysis of transcriptomes for their functional characterization remains a challenge. Here, we review some important aspects of lncRNA biology, focusing on their role as regulatory elements in gene expression modulation during physiological and disease processes, with implications in host and pathogens physiology, and their role in immune response modulation.
Highlights
The discrepancy of about 20,000 protein-coding genes and over 100,000 different transcripts identified in mammalian transcriptomes highlights the possibility of discovering a novel class of non-translated RNAs [1], beyond those already identified in the 1970s, as part of the translation machinery: ribosomal RNAs [2] and transfer RNAs [3]
The central dogma of biology changed with the discovery of functional Non-coding RNAs (ncRNAs) molecules, such as ribosomal RNAs (rRNAs) and transfer RNAs (tRNAs)
After many observations were initially treated with distrust by the scientific community, the importance of these ncRNAs was demonstrated by their functionality, mainly in gene expression regulation
Summary
The discrepancy of about 20,000 protein-coding genes and over 100,000 different transcripts identified in mammalian transcriptomes highlights the possibility of discovering a novel class of non-translated RNAs [1], beyond those already identified in the 1970s, as part of the translation machinery: ribosomal RNAs (rRNAs) [2] and transfer RNAs (tRNAs) [3]. Recent studies estimated that more than half of the expressed lncRNAs are in the cytoplasm, associated with polysome fractions, controlling stability, and translation of mRNAs [40] These data indicate that lncRNA localization depends on the motifs signatures: protein signal-peptides, nuclear-restricted lincRNA BMP/OP-responsive gene (BORG) [41], and Alu-related sequences in a more generally-spread nuclear retention mechanism [42]. In 2010, a group used a high-throughput approach describing the whole transcriptome structure of Saccharomyces cerevisiae at nucleotide resolution [43] These conformations have been unveiled using diverse techniques, such as fragmentation sequencing (FragSeq), which is based on sequencing of fragments digested by single- or double-strand specific nucleases [44], which can be useful in the description of RNA molecular structure and in the identification of folding domains that mediate interaction with other macromolecules. Some tools can predict sites responsible for editing and the impact on structure and function, such as interaction with miRNAs [51]
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