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<p>Small noncoding RNAs (sncRNAs) are subject to 3’-end trimming and tailing activities that impact maturation versus degradation decisions during biogenesis. To investigate the dynamics of human sncRNA 3’-end processing at a global level, we performed genome-wide 3’-end sequencing of newly transcribed and steady-state sncRNAs. This revealed widespread post-transcriptional adenylation of newly transcribed sncRNAs, which came in two distinct varieties. One is characterized by oligoadenylation, which is transient, promoted by TENT4A/4B polymerases, and most commonly observed on unstable small nucleolar RNAs that are not fully processed at their 3’-ends. The other is characterized by monoadenylation, which is broadly catalyzed by TENT2 and, in contrast to oligoadenylation, stably accumulates at the 3’-end of sncRNAs, including Polymerase-III-transcribed (Pol-III) RNAs and a subset of small nuclear RNAs. Monoadenylation inhibits Pol-III RNA post-transcriptional 3’-uridine trimming and extension and, in the case of 7SL RNAs, prevents their accumulation with nuclear La protein and promotes their biogenesis towards assembly into cytoplasmic signal recognition particles. Thus, the biogenesis of human sncRNAs involves widespread mono- or oligoadenylation with divergent impacts on sncRNA fates.</p>

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Widespread mono- and oligoadenylation direct small noncoding RNA maturation versus degradation fates

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月5日

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  • Cody Ocheltree,
  • Blake Skrable,
  • Anastasia Pimentel,
  • Timothy Nicholson-Shaw,
  • Suzanne R Lee,
  • Jens Lykke-Andersen

摘要

Small noncoding RNAs (sncRNAs) are subject to 3’-end trimming and tailing activities that impact maturation versus degradation decisions during biogenesis. To investigate the dynamics of human sncRNA 3’-end processing at a global level, we performed genome-wide 3’-end sequencing of newly transcribed and steady-state sncRNAs. This revealed widespread post-transcriptional adenylation of newly transcribed sncRNAs, which came in two distinct varieties. One is characterized by oligoadenylation, which is transient, promoted by TENT4A/4B polymerases, and most commonly observed on unstable small nucleolar RNAs that are not fully processed at their 3’-ends. The other is characterized by monoadenylation, which is broadly catalyzed by TENT2 and, in contrast to oligoadenylation, stably accumulates at the 3’-end of sncRNAs, including Polymerase-III-transcribed (Pol-III) RNAs and a subset of small nuclear RNAs. Monoadenylation inhibits Pol-III RNA post-transcriptional 3’-uridine trimming and extension and, in the case of 7SL RNAs, prevents their accumulation with nuclear La protein and promotes their biogenesis towards assembly into cytoplasmic signal recognition particles. Thus, the biogenesis of human sncRNAs involves widespread mono- or oligoadenylation with divergent impacts on sncRNA fates.