Genome-wide identification of short 2′,3′-cyclic phosphate-containing RNAs and their regulation in aging

English version

Autoři: Megumi Shigematsu ^aff001; Keisuke Morichika ^aff001; Takuya Kawamura ^aff001; Shozo Honda ^aff001; Yohei Kirino ^aff001
Působiště autorů: Computational Medicine Center, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America ^aff001
Vyšlo v časopise: Genome-wide identification of short 2′,3′-cyclic phosphate-containing RNAs and their regulation in aging. PLoS Genet 15(11): e32767. doi:10.1371/journal.pgen.1008469
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008469

Souhrn

RNA molecules generated by ribonuclease cleavage sometimes harbor a 2′,3′-cyclic phosphate (cP) at their 3′-ends. Those cP-containing RNAs (cP-RNAs) form a hidden layer of transcriptome because standard RNA-seq cannot capture them as a result of cP’s prevention of an adapter ligation reaction. Here we provide genome-wide analyses of short cP-RNA transcriptome across multiple mouse tissues. Using cP-RNA-seq that can exclusively sequence cP-RNAs, we identified numerous novel cP-RNA species which are mainly derived from cytoplasmic tRNAs, mRNAs, and rRNAs. Determination of the processing sites of substrate RNAs for cP-RNA generation revealed highly-specific RNA cleavage events between cytidine and adenosine in cP-RNA biogenesis. cP-RNAs were not evenly derived from the overall region of substrate RNAs but rather from specific sites, implying that cP-RNAs are not from random degradation but are produced through a regulated biogenesis pathway. The identified cP-RNAs were abundantly accumulated in mouse tissues, and the expression levels of cP-RNAs showed age-dependent reduction. These analyses of cP-RNA transcriptome unravel a novel, abundant class of non-coding RNAs whose expression could have physiological roles.

Klíčová slova:

Mammalian genomics – Non-coding RNA – Non-coding RNA sequences – Ribosomal RNA – RNA sequencing – Sequence assembly tools – Transfer RNA – Small nucleolar RNA

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