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Review
. 2018;15(8):1025-1031.
doi: 10.1080/15476286.2018.1511675. Epub 2018 Sep 10.

Non-coding Transcript Variants of Protein-Coding Genes - What Are They Good For?

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Free PMC article
Review

Non-coding Transcript Variants of Protein-Coding Genes - What Are They Good For?

Sonam Dhamija et al. RNA Biol. .
Free PMC article

Abstract

The total number of protein-coding genes in the human genome is not significantly higher than those in much simpler eukaryotes, despite a general increase in genome size proportionate to the organismal complexity. The large non-coding transcriptome and extensive differential splicing, are increasingly being accepted as the factors contributing to the complex mammalian physiology and architecture. Recent studies reveal additional layers of functional complexity: some long non-coding RNAs have been re-defined as micropeptide or microprotein encoding transcripts, and in turn some protein-coding RNAs are bifunctional and display also non-coding functions. Moreover, several protein-coding genes express long non-coding RNA splice-forms and generate circular RNAs in addition to their canonical mRNA transcripts, revoking the strict definition of a gene as coding or non-coding. In this mini review, we discuss the current understanding of these hybrid genes and their possible roles and relevance.

Keywords: ceRNA; circRNA; cncRNAs; lncRNAs; non-coding RNA; smORF; splicing; translation.

Figures

Figure 1.
Figure 1.
Can genes be strictly classified as coding and non-coding? Gene with multiple exons can be transcribed and spliced to generate an mRNA, which is translated to protein, which determines it’s cellular function. In some cases, the mRNAs can additionally have regulatory functions independent of translation. These protein-coding RNAs are classified as cncRNAs (coding/non-coding RNAs). The same gene can also generate long non-coding transcripts by alternative splicing. These lncRNAs can be genuine "non-coding RNAs" with regulatory functions or they can harbor smORFs (small ORFs) which encode micro-peptides. Back-splicing can also generate circRNAs (circular RNAs) from several genes. While circRNAs are usually stable non-coding RNAs with regulatory function, recent evidences suggest that at least some of them could be translated.
Figure 2.
Figure 2.
Roles of ``non-coding‘‘ variants arising from protein-coding genes. (a). Intron retention could lead to the generation of nuclear lncRNA intermediates which can undergo signal-induced posttranscriptional splicing to translatable mRNAs, which are then exported from the nucleus. (b). Some lncRNA transcript variants and circRNAs function as miRNA sponges, facilitating efficient translation of mRNAs. (c) lncRNAs and circRNAs compete with mRNAs for binding to regulatory RNA-binding proteins (RBPs), sequester RBPs and alter the translation and stability of mRNAs. (d). mRNAs and smORF-containing transcript variants could encode full-length proteins and truncated micropeptides respectively. Some micropeptides could function as miPs (microProteins) and interfere with full length protein function, owing to their common origins and sequence identity.

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