Exploring the expanding universe of small RNAs

Abstract

mall noncoding RNAs (sncRNAs) are universally distributed in all kingdoms of life-from bacteria and archaea to various eukaryotic organisms 1-3 -and have not ceased to surprise us throughout the last two decades regarding their compositional and functional diversity. Although the definition of 'small' is relatively empirical and subjective in different contexts, in this paper we mainly discuss sncRNAs of 15-50 nucleotides (nt) in length, including the relatively well-characterized small interfering RNAs (siRNAs, 20-27 nt), microRNAs (miRNAs, 21-23 nt) and Piwi-interacting RNAs (piRNAs, 21-35 nt) [4][5][6] , but with more focus on more recently discovered non-canonical sncRNAs (15-50 nt) that are derived from longer structured RNAs 7 such as transfer RNA (tRNA) 8,9 , ribosomal RNA (rRNA) 10,11 , Y RNA (yRNA) 11,12 , small nuclear RNA (snRNA) 13,14 , small nucleolar RNAs (snoRNA) 15,16 , vault RNA (vtRNA) 17,18 and even messenger RNA (mRNA) 19,20 . Studies on non-canonical sncRNAs have recently gained momentum, exemplified by the new focus on tRNA-derived small RNA (tsRNA) 8 , and are expected to expand to other categories with their systematic discovery. To facilitate communication and reduce confusion, we propose a unified naming system for these non-canonical sncRNAs (Box 1) when describing discoveries from different laboratories (usually using different names).Like many noncoding RNAs in history, the emerging non-canonical sncRNAs were initially considered as merely random degradation products of RNA turnover/metabolism and thus neglected, yet increasing evidence has begun to put them in the spotlight as regulatory sncRNAs 8,21 . This is partly due to the revelation that they are regulated by both genetic and environmental factors 18,[22][23][24][25][26][27] and that many of them are functional and associated with multiple diseases-including those linked to cancer [28][29][30] , immunity 12,31 , viral infection 32,33 , neurological disorders 34,35 , stem cells 26,[36][37][38][39] , retrotransposon control 40,41 and epigenetic inheritance 24,25,[42][43][44][45] as well as because in many cases, the exertion of their function depends on mechanisms that are distinct from those of well-studied siRNAs, miRNAs or piRNAs. Moreover, it was recently recognized that many non-canonical sncRNAs harbour various RNA modifications, some of which can prevent the detection of sncRNAs by traditional RNA sequencing (RNA-seq) 10,14,46,47 . This has promoted a recent wave of method improvements, leading to their comprehensive discovery and identification, which have in turn ignited interest in research centred on sncRNA modifications 48 . Here we briefly outline the biogenesis and functional principles of non-canonical sncRNAs and discuss recent methodological developments in promoting sncRNA discovery and accurate expression analyses as well as new techniques for direct multiplexed mapping of RNA modifications, which is necessary for decoding the full function of sncRNAs.

A role for Flipons and miRNAs in Promoter Specification during Development

“…However, survival does not depend on the AGO2 enzymatic slicer activity needed to suppress translation as mice homozygous for a catalytically dead Ago2 ADH allele develop normally [6], suggesting that AGO2 is active through a different mechanism. Besides the cytoplasm, miRNAs also localize to the nucleus [2,7]. They modulate gene expression [2,8,9] and potentially a subset of alternative splices [10][11][12].…”

“…Besides the cytoplasm, miRNAs also localize to the nucleus [2,7]. They modulate gene expression [2,8,9] and potentially a subset of alternative splices [10][11][12].…”

Current Status of Regulatory Non-Coding RNAs Research in the Tritryp

“…The specific cleavage of canonical ncRNAs which produce fragments that functionally mimic miRNAs or directly interact with ribosomes, proteins (such as RNA binding proteins), or other RNAs to modulate gene expression [ 28 , 29 , 30 ]. Although these fragments were initially considered products of degradation and thus ignored in small RNA-seq analysis, the accumulated evidence supports the generation of fragments by specific processing of ncRNA [ 31 , 32 , 33 ]. However, many cases lack known processing factors or defined mechanisms of action, leaving an open field for research ahead.…”

The expression and function of 28s5-rtsRNA: an update

“…Along with the development of small RNA high-throughput sequencing (HTS) technology, the repertoire of small RNAs was greatly expanded [1][2][3][4][5]. In addition to well-characterized microRNAs and piRNAs, small RNAs were found to be originated from abundant housekeeping non-coding RNAs, such as tRNAs, rRNAs, and snoRNAs [1][2][3][4][5][6].…”

“…Along with the development of small RNA high-throughput sequencing (HTS) technology, the repertoire of small RNAs was greatly expanded [1][2][3][4][5]. In addition to well-characterized microRNAs and piRNAs, small RNAs were found to be originated from abundant housekeeping non-coding RNAs, such as tRNAs, rRNAs, and snoRNAs [1][2][3][4][5][6]. Recently, ample research has been focused on tRNA-derived small RNAs (tsRNAs) and revealed its diverse functions, including promoting stress-induced translational repression [7,8], mediating epigenetic inheritance of paternally acquired traits [9][10][11], inhibiting cell apoptosis [12] and so on [13,14].…”