Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing

Fei Teng; Chen Yiwen; Xiao TengfeiLi WeiCato LauraZhang PengCotter Maura B.Bowden MichaelaLis Rosina T.Zhao Shuang G.Wu QiuFeng Felix Y.Loda MassimoHe Housheng HansenLiu X. ShirleyBrown Myles

首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America. >Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing

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Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing

机译：Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing

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Alternative RNA splicing plays an important role in cancer. To determine which factors involved in RNA processing are essential in prostate cancer, we performed a genome-wide CRISPR/Cas9 knockout screen to identify the genes that are required for prostate cancer growth. Functional annotation defined a set of essential spliceosome and RNA binding protein (RBP) genes, including most notably heterogeneous nuclear ribonucleoprotein L (HNRNPL). We defined the HNRNPL-bound RNA landscape by RNA immunoprecipitation coupled with next-generation sequencing and linked these RBP-RNA interactions to changes in RNA processing. HNRNPL directly regulates the alternative splicing of a set of RNAs, including those encoding the androgen receptor, the key lineage-specific prostate cancer oncogene. HNRNPL also regulates circular RNA formation via back splicing. Importantly, both HNRNPL and its RNA targets are aberrantly expressed in human prostate tumors, supporting their clinical relevance. Collectively, our data reveal HNRNPL and its RNA clients as players in prostate cancer growth and potential therapeutic targets.

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来源
《Proceedings of the National Academy of Sciences of the United States of America.》 |2017年第26期|E5207-E5215|共9页
作者
Fei Teng; Chen Yiwen; Xiao TengfeiLi WeiCato LauraZhang PengCotter Maura B.Bowden MichaelaLis Rosina T.Zhao Shuang G.Wu QiuFeng Felix Y.Loda MassimoHe Housheng HansenLiu X. ShirleyBrown Myles;
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作者单位

Northeastern Univ, Coll Life & Hlth Sci, Shenyang 110819, Peoples R China;

Univ Texas MD Anderson Canc Ctr, Div Quantitat Sci, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA;

Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Dept Med Oncol, Div Mol & Cellular Oncol, Boston, MA 02215 USADana Farber Canc Inst, Ctr Funct Canc Epigenet, Dept Biostat & Computat Biol, Boston, MA 02215 USADana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USAUniv Michigan, Ctr Comprehens Canc, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USATongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai 200092, Peoples R ChinaUniv Hlth Network, Princess Margaret Canc Ctr, Toronto, ON M5G 1L7, Canada;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
CRISPR screen; HNRNPL; prostate cancer; RNA binding protein; alternative splicing;

Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing

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