The RNA Binding Protein Quaking Regulates Formation of circRNAs

被引：1888

作者：

Conn, Simon J. ^{[1
,2
]}

Pillman, Katherine A. ^{[1
,2
,3
]}

Toubia, John ^{[1
,2
,3
]}

Conn, Vanessa M. ^{[1
,2
]}

Salmanidis, Marika ^{[1
,2
]}

Phillips, Caroline A. ^{[1
,2
,4
]}

Roslan, Suraya ^{[1
,2
]}

Schreiber, Andreas W. ^{[1
,2
,3
,4
]}

Gregory, Philip A. ^{[1
,2
,5
]}

Goodall, Gregory J. ^{[1
,2
,4
,5
]}

机构：

[1] SA Pathol, Ctr Canc Biol, Adelaide, SA 5000, Australia

[2] Univ S Australia, Adelaide, SA 5000, Australia

[3] SA Pathol, ACRF Canc Genom Facil, Adelaide, SA 5000, Australia

[4] Univ Adelaide, Sch Mol & Biomed Sci, Adelaide, SA 5005, Australia

[5] Univ Adelaide, Dept Med, Adelaide, SA 5005, Australia

来源：

CELL | 2015年 / 160卷 / 06期

基金：

英国医学研究理事会;

关键词：

CIRCULAR RNAS; MESSENGER-RNA; MESENCHYMAL TRANSITION; FAMILY; IDENTIFICATION; TRANSCRIPTS; MECHANISMS; GENE;

D O I：

10.1016/j.cell.2015.02.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Circular RNAs (circRNAs), formed by non-sequential back-splicing of pre-mRNA transcripts, are a widespread form of non-coding RNA in animal cells. However, it is unclear whether the majority of circRNAs represent splicing by-products without function or are produced in a regulated manner to carry out specific cellular functions. We show that hundreds of circRNAs are regulated during human epithelial-mesenchymal transition (EMT) and find that the production of over one-third of abundant circRNAs is dynamically regulated by the alternative splicing factor, Quaking (QKI), which itself is regulated during EMT. Furthermore, by modulating QKI levels, we show the effect on circRNA abundance is dependent on intronic QKI binding motifs. Critically, the addition of QKI motifs is sufficient to induce de novo circRNA formation from transcripts that are normally linearly spliced. These findings demonstrate circRNAs are both purposefully synthesized and regulated by cell-type specific mechanisms, suggesting they play specific biological roles in EMT.

引用

页码：1125 / 1134

页数：10

共 41 条

[41] Complementary Sequence-Mediated Exon Circularization [J].

Zhang, Xiao-Ou ;

Wang, Hai-Bin ;

Zhang, Yang ;

Lu, Xuhua ;

Chen, Ling-Ling ;

Yang, Li .

CELL, 2014, 159 (01) :134-147

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