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The Output of Protein-Coding Genes Shifts to Circular RNAs When the Pre-mRNA Processing Machinery Is Limiting

Molecular cell, 2017-12, Vol.68 (5), p.940-954.e3 [Peer Reviewed Journal]

2017 Elsevier Inc. ;Copyright © 2017 Elsevier Inc. All rights reserved. ;ISSN: 1097-2765 ;EISSN: 1097-4164 ;DOI: 10.1016/j.molcel.2017.10.034 ;PMID: 29174924

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Title:
The Output of Protein-Coding Genes Shifts to Circular RNAs When the Pre-mRNA Processing Machinery Is Limiting
Author: Liang, Dongming ; Tatomer, Deirdre C. ; Luo, Zheng ; Wu, Huang ; Yang, Li ; Chen, Ling-Ling ; Cherry, Sara ; Wilusz, Jeremy E.
Subjects: Animals ; backsplicing ; Cell Line ; circRNA ; cleavage/polyadenylation ; Drosophila melanogaster - genetics ; Drosophila melanogaster - metabolism ; Drosophila Proteins - biosynthesis ; Drosophila Proteins - genetics ; exon definition ; Laccase - biosynthesis ; Laccase - genetics ; Laccase2 ; Pladienolide B ; pre-mRNA splicing ; Ribonucleoproteins, Small Nucleolar - genetics ; Ribonucleoproteins, Small Nucleolar - metabolism ; RNA - biosynthesis ; RNA - genetics ; RNA Interference ; RNA Polymerase II - metabolism ; RNA Precursors - biosynthesis ; RNA Precursors - genetics ; RNA Splicing ; RNA Splicing Factors - genetics ; RNA Splicing Factors - metabolism ; RNA Stability ; RNA, Circular ; RNA, Messenger - biosynthesis ; RNA, Messenger - genetics ; SF3b1 ; spliceosome ; Spliceosomes - genetics ; Spliceosomes - metabolism ; transcription termination ; Transcription Termination, Genetic ; Transcription, Genetic ; Transfection
Is Part Of: Molecular cell, 2017-12, Vol.68 (5), p.940-954.e3
Description: Many eukaryotic genes generate linear mRNAs and circular RNAs, but it is largely unknown how the ratio of linear to circular RNA is controlled or modulated. Using RNAi screening in Drosophila cells, we identify many core spliceosome and transcription termination factors that control the RNA outputs of reporter and endogenous genes. When spliceosome components were depleted or inhibited pharmacologically, the steady-state levels of circular RNAs increased while expression of their associated linear mRNAs concomitantly decreased. Upon inhibiting RNA polymerase II termination via depletion of the cleavage/polyadenylation machinery, circular RNA levels were similarly increased. This is because readthrough transcripts now extend into downstream genes and are subjected to backsplicing. In total, these results demonstrate that inhibition or slowing of canonical pre-mRNA processing events shifts the steady-state output of protein-coding genes toward circular RNAs. This is in part because nascent RNAs become directed into alternative pathways that lead to circular RNA production. [Display omitted] •RNAi screen identifies pre-mRNA processing factors that modulate circular RNA levels•Circular RNA expression increases when core spliceosomal components are depleted•Backsplicing can occur in conditions that inhibit canonical mRNA splicing events•Readthrough transcription enables production of circular RNAs from downstream genes Many protein-coding genes produce linear mRNAs and circular RNAs. Liang et al. find that circular RNAs become the preferred gene output when core spliceosome or transcription termination factors are depleted from cells. This is in part because nascent RNAs are directed into alternative pathways that lead to circular RNA biogenesis.
Publisher: United States: Elsevier Inc
Language: English
Identifier: ISSN: 1097-2765
EISSN: 1097-4164
DOI: 10.1016/j.molcel.2017.10.034
PMID: 29174924
Source: MEDLINE
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The Output of Protein-Coding Genes Shifts to Circular RNAs When the Pre-mRNA Processing Machinery Is Limiting

2017 Elsevier Inc. ;Copyright © 2017 Elsevier Inc. All rights reserved. ;ISSN: 1097-2765 ;EISSN: 1097-4164 ;DOI: 10.1016/j.molcel.2017.10.034 ;PMID: 29174924

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