Structured elements drive extensive circular RNA translation

被引：197

作者：

Chen, Chun-Kan ^{[1
,2
,3
]}

Cheng, Ran ^{[4
,5
]}

Demeter, Janos ^{[4
,5
]}

Chen, Jin ^{[6
,7
]}

Weingarten-Gabbay, Shira ^{[8
,9
]}

Jiang, Lihua ^{[3
]}

Snyder, Michael P. ^{[3
]}

Weissman, Jonathan S. ^{[10
,11
]}

Segal, Eran ^{[8
,9
]}

Jackson, Peter K. ^{[4
,5
]}

Chang, Howard Y. ^{[1
,2
,3
,12
]}

机构：

[1] Stanford Univ, Ctr Personal Dynam Regulomes, Stanford, CA 94305 USA

[2] Stanford Univ, Sch Med, Dept Dermatol, Stanford, CA 94305 USA

[3] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA

[4] Stanford Univ, Baxter Lab, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA

[5] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA

[6] Univ Texas Southwestern Med Ctr Dallas, Dept Pharmacol, Dallas, TX 75390 USA

[7] Univ Texas Southwestern Med Ctr Dallas, Cecil H & Ida Green Ctr Reprod Biol Sci, Dallas, TX 75390 USA

[8] Weizmann Inst Sci, Dept Comp Sci & Appl Math, IL-76100 Rehovot, Israel

[9] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel

[10] Whitehead Inst Biomed Res, Cambridge, MA 02139 USA

[11] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA

[12] Stanford Univ, Howard Hughes Med Inst, Sch Med, Stanford, CA 94305 USA

来源：

MOLECULAR CELL | 2021年 / 81卷 / 20期

关键词：

18S RIBOSOMAL-RNA; CAP-INDEPENDENT TRANSLATION; EUKARYOTIC MESSENGER-RNA; GENOME-WIDE ANALYSIS; PROTEIN-SYNTHESIS; 80S RIBOSOME; IN-VIVO; MEDIATED TRANSLATION; INHIBITS TRANSLATION; NONCODING RNAS;

D O I：

10.1016/j.molcel.2021.07.042

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：

The human genome encodes tens of thousands circular RNAs (circRNAs) with mostly unknown functions. Circular RNAs require internal ribosome entry sites (IRES) if they are to undergo translation without a 5' cap. Here, we develop a high-throughput screen to systematically discover RNA sequences that can direct circRNA translation in human cells. We identify more than 17,000 endogenous and synthetic sequences as candidate circRNA IRES. 18S rRNA complementarity and a structured RNA element positioned on the IRES are important for driving circRNA translation. Ribosome profiling and peptidomic analyses show extensive IRES-ribosome association, hundreds of circRNA-encoded proteins with tissue-specific distribution, and antigen presentation. We find that circFGFR1p, a protein encoded by circFGFR1 that is downregulated in cancer, functions as a negative regulator of FGFR1 oncoprotein to suppress cell growth during stress. Systematic identification of circRNA IRES elements may provide important links among circRNA regulation, biological function, and disease.

引用

页码：4300 / +

页数：33

共 140 条

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