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Review
, 42 (5), 379-385

Non-Coding RNAs in Caenorhabditis elegans Aging

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Review

Non-Coding RNAs in Caenorhabditis elegans Aging

Sieun S Kim et al. Mol Cells.

Abstract

Non-coding RNAs (ncRNAs) comprise various RNA species, including small ncRNAs and long ncRNAs (lncRNAs). ncRNAs regulate various cellular processes, including transcription and translation of target messenger RNAs. Recent studies also indicate that ncRNAs affect organismal aging and conversely aging influences ncRNA levels. In this review, we discuss our current understanding of the roles of ncRNAs in aging and longevity, focusing on recent advances using the roundworm Caenorhabditis elegans. Expression of various ncRNAs, including microRNA (miRNA), tRNA-derived small RNA (tsRNA), ribosomal RNA (rRNA), PIWI-interacting RNA (piRNA), circular RNA (circRNA), and lncRNA, is altered during aging in C. elegans. Genetic modulation of specific ncRNAs affects longevity and aging rates by modulating established aging-regulating protein factors. Because many aging-regulating mechanisms in C. elegans are evolutionarily conserved, these studies will provide key information regarding how ncRNAs modulate aging and lifespan in complex organisms, including mammals.

Keywords: Caenorhabditis elegans; aging; lifespan; non-coding RNA; small RNA.

Figures

Fig. 1
Fig. 1. Biogenesis of several types of non-coding RNAs: miRNA, tsRNA, rRNA and circRNA
(A) miRNAs are first transcribed to pri-miRNAs by RNA polymerase II (Pol II). Nuclear Drosha (C. elegans DRSH-1)-DGCR8 (C. elegans PASH-1) complex then cleaves pri-miRNAs for conversion to pre-miRNAs. Next, pre-miRNAs are translocated from the nucleus to the cytosol, for cleavage by Dicer (C. elegans DCR-1). One of the strands then forms miRNA-induced silencing complex (miRISC) with Argonaute proteins that unwind the RNA duplex. (B) tRNAs are transcribed by RNA polymerase III (Pol III) to precursor tRNA (pre-tRNA) transcripts, which have 5′-leader and 3′-trailer sequences. The 5′-leader sequence is cleaved by endoribonuclease P (RNase P) and the 3′-trailer sequence is removed by endonuclease Z (RNase Z) for generating mature tRNAs. Dicer may cleave the mature tRNAs to tRNA-derived fragments (tRFs). In mammals, angiogenin (ANG, ribonuclease A) cleaves tRNAs and generates tRNA-derived stress-induced RNAs (tiRNAs), also known as tRNA halves, tRNA halftypes of tRNA-derived small RNAs (tsRNAs). (C) RNA polymerase I (Pol I) transcribes 18S, 5.8S, and 28S rRNAs in the nucleolus, whereas 5S rRNA is transcribed by Pol III in the nucleus. (D) Circular RNAs (circRNAs) are produced by back-splicing of precursor mRNAs that are transcribed by Pol II.
Fig. 2
Fig. 2. Age-dependent expression changes in C. elegans non-coding RNAs
Total microRNA (miRNA) and PIWI-interacting RNA (piRNA) levels are gradually decreased during C. elegans aging. In contrast, tRNA-derived small RNA (tsRNA), ribosomal RNA (rRNA) and circular RNA (circRNA) levels generally display age-dependent increases.

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