Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing Academic Article uri icon

Overview

MeSH Major

  • CRISPR-Cas Systems
  • Gene Expression Regulation, Neoplastic
  • Genome-Wide Association Study
  • Neoplasm Proteins
  • Prostatic Neoplasms
  • RNA Splicing
  • RNA, Neoplasm
  • Ribonucleoproteins

abstract

  • 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.

publication date

  • June 27, 2017

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC5495225

Digital Object Identifier (DOI)

  • 10.1073/pnas.1617467114

PubMed ID

  • 28611215

Additional Document Info

start page

  • E5207

end page

  • E5215

volume

  • 114

number

  • 26