ncRNAs

Non-coding RNAs (ncRNAs) are RNA molecules transcribed from the genome that do not serve as templates for protein synthesis. Although once thought to be transcriptional noise, ncRNAs are now recognized as key regulators of gene expression and genome integrity. They range from small RNAs a few nucleotides long to long non-coding RNAs that span thousands of bases.

Major categories include housekeeping ncRNAs, such as ribosomal RNA (rRNA) and transfer RNA (tRNA), which are essential components of protein synthesis, and a broad array of regulatory ncRNAs. Regulatory small ncRNAs include microRNAs (miRNAs), which modulate mRNA stability and translation; small interfering RNAs (siRNAs), which mediate RNA interference; and Piwi-interacting RNAs (piRNAs), which suppress transposable elements in the germ line. Other small nucleolar RNAs (snoRNAs) guide chemical modifications of rRNAs and other RNAs. Long non-coding RNAs (lncRNAs) are diverse in origin and function, often acting as guides, scaffolds, or decoys in gene regulatory networks.

Biogenesis varies by class. rRNA and tRNA are transcribed by RNA polymerase I and III respectively; miRNAs and siRNAs derive from precursor transcripts processed by Drosha and Dicer and are incorporated into Argonaute-containing complexes to regulate target RNAs; piRNAs originate from distinct pathways and associate with Piwi proteins. LncRNAs are typically transcribed by RNA polymerase II and frequently undergo splicing and polyadenylation. Functions include chromatin remodeling, transcriptional regulation, post-transcriptional control of mRNA, RNA modification, and genome defense against repeats and viruses.

ncRNAs are studied across organisms and are identified through RNA sequencing and complementary methods, though annotation is complicated by limited sequence conservation and tissue-specific expression. They are implicated in development, differentiation, aging, and disease, including cancer and neurodegeneration. Understanding ncRNAs provides insight into regulatory complexity beyond protein-coding genes.