Non-coding RNAs: multi-tasking molecules in the cell

Abstract

In the last years it has become increasingly clear that the mammalian transcriptome is highly complex and includes a large number of small non-coding RNAs (sncRNAs) and long noncoding RNAs (lncRNAs). Here we review the biogenesis pathways of the three classes of sncRNAs, namely short interfering RNAs (siRNAs), microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs). These ncRNAs have been extensively studied and are involved in pathways leading to specific gene silencing and the protection of genomes against virus and transposons, for example. Also, lncRNAs have emerged as pivotal molecules for the transcriptional and post-transcriptional regulation of gene expression which is supported by their tissue-specific expression patterns, subcellular distribution, and developmental regulation. Therefore, we also focus our attention on their role in differentiation and development. SncRNAs and lncRNAs play critical roles in defining DNA methylation patterns, as well as chromatin remodeling thus having a substantial effect in epigenetics. The identification of some overlaps in their biogenesis pathways and functional roles raises the hypothesis that these molecules play concerted functions in vivo, creating complex regulatory networks where cooperation with regulatory proteins is necessary. We also highlighted the implications of biogenesis and gene expression deregulation of sncRNAs and lncRNAs in human diseases like cancer.

Figure 1

Gene silencing: mRNA post-transcriptional regulation by lncRNA and miRNA. lncRNAs can be transcribed as natural antisense transcripts, from the same loci (cis-NAT, the same gene is transcribed in both directions) or from a different loci (trans-NAT, for example from a pseudogene). These NATs transcripts can pair with the coding transcripts, originating dsRNA molecules that will activate the siRNA machinery leading to mRNA degradation. miRNAs are also complementary of coding mRNAs and can pair with a perfect match leading to the activation of the siRNA machinery or they can pair with gaps leading to translation interference.

Figure 2

Diagram of functional relationships among lncRNAs, siRNAs, miRNas and piRNAs. This “venn diagram” depicts the specific function of each RNA molecule (inside each circle) as well as the shared functions (overlapping areas). Some of the disorders caused by deregulation in the expression patterns of these RNA molecules are indicated outside the circles.