Upstream open reading frames: new players in the landscape of cancer gene regulation

Author:

Dasgupta Anwesha123ORCID,Prensner John R123ORCID

Affiliation:

1. Chad Carr Pediatric Brain Tumor Center, University of Michigan Medical School , Ann Arbor , MI  48109 , USA

2. Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Michigan Medical School , Ann Arbor , MI  48109 , USA

3. Department of Biological Chemistry, University of Michigan Medical School , Ann Arbor , MI  48109 , USA

Abstract

Abstract The translation of RNA by ribosomes represents a central biological process and one of the most dysregulated processes in cancer. While translation is traditionally thought to occur exclusively in the protein-coding regions of messenger RNAs (mRNAs), recent transcriptome-wide approaches have shown abundant ribosome activity across diverse stretches of RNA transcripts. The most common type of this kind of ribosome activity occurs in gene leader sequences, also known as 5′ untranslated regions (UTRs) of the mRNA, that precede the main coding sequence. Translation of these upstream open reading frames (uORFs) is now known to occur in upwards of 25% of all protein-coding genes. With diverse functions from RNA regulation to microprotein generation, uORFs are rapidly igniting a new arena of cancer biology, where they are linked to cancer genetics, cancer signaling, and tumor-immune interactions. This review focuses on the contributions of uORFs and their associated 5′UTR sequences to cancer biology.

Funder

National Institutes of Health

National Cancer Institute

Alex's Lemonade Stand Foundation Young Investigator Award

St. Baldrick's Foundation Scholar Award

Hyundai Hope on Wheels Foundation

Yuvaan Tiwari Foundation

DIPG/DMG Research Funding Alliance

Hope Foundation

Curing Kids Cancer Foundation

Andrew McDonough B+ Foundation

Collaborative Pediatric Cancer Research Awards Program

Kids Join the Fight award

Publisher

Oxford University Press (OUP)

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