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Widespread mono- and oligoadenylation direct small noncoding RNA maturation versus degradation fates
Cody Ocheltree1, Blake Skrable1, Anastasia Pimentel1
1Department of Molecular Biology, School of Biological Sciences, University of California San Diego, La Jolla, CA, 92093, USA.
Biorxiv : the Preprint Server for Biology
|February 20, 2025
Summary
Human small non-coding RNAs (sncRNAs) undergo 3' end adenylation, impacting their stability and function. This study reveals two types of adenylation, oligoadenylation and monoadenylation, with distinct roles in sncRNA biogenesis.
Area of Science:
- Molecular Biology
- RNA Biology
- Gene Regulation
Background:
- Small non-coding RNAs (sncRNAs) are crucial regulators of gene expression.
- Their biogenesis involves complex processing steps, including 3' end modifications.
- Post-transcriptional modifications like trimming and tailing influence sncRNA fate.
Purpose of the Study:
- To globally investigate the dynamics of human sncRNA 3' end processing.
- To identify and characterize different types of 3' end adenylation in nascent and steady-state sncRNAs.
- To understand the functional consequences of these modifications on sncRNA biogenesis.
Main Methods:
- Genome-wide 3' end sequencing of nascently-transcribed and steady-state sncRNAs.
- Analysis of adenylation patterns and associated RNA polymerases (TENT4A/4B, TENT2).
- Investigation of the impact of monoadenylation on Pol-III RNA processing and 7SL RNA biogenesis.
Main Results:
- Widespread post-transcriptional adenylation of nascent sncRNAs was observed.
- Two distinct types of adenylation were identified: transient oligoadenylation (TENT4A/4B, linked to unstable snoRNAs) and stable monoadenylation (TENT2, found on Pol-III RNAs and some snRNAs).
- Monoadenylation inhibits 3' uridine modification of Pol-III RNAs and promotes 7SL RNA biogenesis for signal recognition particle assembly.
Conclusions:
- Human sncRNA biogenesis involves extensive mono- and oligoadenylation.
- These modifications have divergent impacts on sncRNA stability, processing, and ultimate function.
- Adenylation represents a key regulatory mechanism controlling sncRNA fate.
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