SAFB2 Enables the Processing of Suboptimal Stem-Loop Structures in Clustered Primary miRNA Transcripts.
Animals
Cell Line
Cell Nucleus
/ metabolism
HEK293 Cells
Humans
Inverted Repeat Sequences
/ genetics
Matrix Attachment Region Binding Proteins
/ genetics
Mice
MicroRNAs
/ genetics
Nuclear Matrix-Associated Proteins
/ genetics
Nucleic Acid Conformation
RNA Processing, Post-Transcriptional
/ genetics
RNA-Binding Proteins
/ metabolism
Receptors, Estrogen
/ genetics
DGCR8
DROSHA
ERH
Microprocessor
SAFB
cluster assistance
miRNA
microRNA
microRNA biogenesis
pri-miRNA processing
Journal
Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571
Informations de publication
Date de publication:
04 06 2020
04 06 2020
Historique:
received:
02
12
2019
revised:
24
03
2020
accepted:
08
05
2020
entrez:
6
6
2020
pubmed:
6
6
2020
medline:
20
9
2020
Statut:
ppublish
Résumé
Many microRNAs (miRNAs) are generated from primary transcripts containing multiple clustered stem-loop structures that are thought to be recognized and cleaved by the Microprocessor complex as independent units. Here, we uncover an unexpected mode of processing of the bicistronic miR-15a-16-1 cluster. We find that the primary miR-15a stem-loop is not processed on its own but that the presence of the neighboring primary miR-16-1 stem-loop on the same transcript can compensate for this deficiency in cis. Using a CRISPR/Cas9 screen, we identify SAFB2 (scaffold attachment factor B2) as an essential co-factor in this miR-16-1-assisted pri-miR-15 cleavage and describe SAFB2 as an accessory protein of the Microprocessor. Notably, SAFB2-mediated cleavage expands to other clustered pri-miRNAs, indicating a general mechanism. Together, our study reveals an unrecognized function of SAFB2 in miRNA processing and suggests a scenario in which SAFB2 enables the binding and processing of suboptimal Microprocessor substrates in clustered primary miRNA transcripts.
Identifiants
pubmed: 32502422
pii: S1097-2765(20)30312-9
doi: 10.1016/j.molcel.2020.05.011
pii:
doi:
Substances chimiques
MIRN15 microRNA, human
0
MIRN16 microRNA, human
0
Matrix Attachment Region Binding Proteins
0
MicroRNAs
0
Nuclear Matrix-Associated Proteins
0
RNA-Binding Proteins
0
Receptors, Estrogen
0
SAFB2 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
876-889.e6Subventions
Organisme : Austrian Science Fund FWF
ID : P 30194
Pays : Austria
Organisme : Austrian Science Fund FWF
ID : P 30196
Pays : Austria
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.