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

TL;DR

The study reveals that small noncoding RNAs in humans undergo mono- or oligoadenylation, which determines whether they mature or degrade.

Contribution

The discovery of widespread mono- and oligoadenylation as key regulators of sncRNA biogenesis fates is novel.

Findings

Oligoadenylation by TENT4A/B is linked to unstable small nucleolar RNAs.

Monoadenylation by TENT2 stabilizes RNA Polymerase-III transcripts and promotes 7SL RNA biogenesis.

Mono- and oligoadenylation have divergent roles in directing sncRNA maturation or degradation.

Abstract

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.

Newly transcribed small non-coding (snc)RNAs undergo maturation or degradation directed by 3’ end trimming and tailing events. This study uncovers widespread mono- and oligo-adenylation during biogenesis of sncRNAs with divergent impacts on maturation versus degradation fates.

Genome-wide 3’ end sequencing of newly transcribed and steady state human small non-coding RNAs reveals widespread mono- and oligo-adenylation associated with biogenesis.Oligoadenylation is promoted by TENT4A/B and associated with partially processed unstable small nucleolar RNAs.Monoadenylation is promoted by TENT2, occurs on RNA Polymerase-III transcripts and a subset of small nuclear RNAs, and persists to the steady state.Monoadenylation by TENT2 terminates 3’ end uridylation and deuridylation dynamics for RNA Polymerase-III transcripts and promotes 7SL RNA biogenesis.

Genome-wide 3’ end sequencing of newly transcribed and steady state human small non-coding RNAs reveals widespread mono- and oligo-adenylation associated with biogenesis.

Oligoadenylation is promoted by TENT4A/B and associated with partially processed unstable small nucleolar RNAs.

Monoadenylation is promoted by TENT2, occurs on RNA Polymerase-III transcripts and a subset of small nuclear RNAs, and persists to the steady state.

Monoadenylation by TENT2 terminates 3’ end uridylation and deuridylation dynamics for RNA Polymerase-III transcripts and promotes 7SL RNA biogenesis.

Global 3’ end profiling of small noncoding RNAs shows TENT2-dependent monoadenylation and TENT4A/B-dependent oligo-adenylation during sncRNA biogenesis.

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