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

Teng Fei1,2,3,4, Yiwen Chen5, Tengfei Xiao2,3,4

  • 1College of Life and Health Sciences, Northeastern University, Shenyang 110819, People's Republic of China; feiteng@mail.neu.edu.cn xsliu@jimmy.harvard.edu myles_brown@dfci.harvard.edu.

Proceedings of the National Academy of Sciences of the United States of America
|June 15, 2017
PubMed

Insights

Heterogeneous nuclear ribonucleoprotein L (HNRNPL) is crucial for prostate cancer growth by regulating RNA splicing and circular RNA formation. Targeting HNRNPL and its RNA clients may offer new therapeutic strategies for prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Alternative RNA splicing is a critical process in cancer development.
  • Identifying key RNA processing factors in prostate cancer is essential for understanding disease progression.

Purpose of the Study:

  • To identify genes essential for prostate cancer growth using a genome-wide CRISPR/Cas9 knockout screen.
  • To investigate the role of heterogeneous nuclear ribonucleoprotein L (HNRNPL) in prostate cancer.

Main Methods:

  • Genome-wide CRISPR/Cas9 knockout screening to identify essential genes.
  • RNA immunoprecipitation coupled with next-generation sequencing (RIP-Seq) to define HNRNPL-bound RNAs.
  • Analysis of RNA processing changes, including alternative splicing and circular RNA formation.

Main Results:

  • A set of essential spliceosome and RNA binding protein (RBP) genes were identified, with HNRNPL being particularly notable.
  • HNRNPL directly regulates alternative splicing of key RNAs, including the androgen receptor.
  • HNRNPL influences circular RNA formation via back splicing.
  • Aberrant expression of HNRNPL and its RNA targets in human prostate tumors indicates clinical relevance.

Conclusions:

  • HNRNPL plays a significant role in prostate cancer growth by modulating RNA processing.
  • HNRNPL and its RNA clients represent potential therapeutic targets for prostate cancer treatment.
Keywords:
CRISPR screenHNRNPLRNA binding proteinalternative splicingprostate cancer

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