A prometastatic splicing program regulated by SNRPA1 interactions with structured RNA elements
Abstract
Cells undergo many genomic changes as they progress toward metastatic cancer. One aspect of this change is to RNA expression and splicing isoforms, but how these differences affect tumor progression is not well characterized. Fish et al. developed a computational framework called pyTEISER that identifies structural cis-regulatory elements that control diverse types of RNA regulation. Applying pyTEISER to models of breast cancer metastasis, they discovered an RNA short-stem-loop element that forms a “structural splicing enhancer” that acts in cis to regulate alternative splicing of RNA transcripts. One of these interactions encompasses the RNA-binding protein SNRPA1 and results in alternative exon inclusion that affects metastatic capacity in xenograft models. Thus, RNA element binding may play a role in splicing regulation and is potentially an important component of the cis-splicing code.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 14, 2021
- Source ID
- 10.1126/science.abc7531
Entities
People
- Albertas Navickas
- Benjamin Hänisch
- Bruce Culbertson
- Claudio R. Alarcón
- Faraz Khosravi Mardakheh
- Hamed S. Najafabadi
- Hani Goodarzi
- Henrik Molina
- Hoang C.B. Nguyen
- Kristle Garcia
- Larisa M. Soto
- Lisa Fish
- Maria Dermit
- Matvei Khoroshkin
- Steven Zhang
Organizations
- American College of Surgeons
- Canadian Institutes of Health Research
- Howard Hughes Medical Institute
- McGill Genome Centre
- McGill University
- Medical Research Council
- National Cancer Institute
- National Institutes of Health
- Queen Mary University of London
- The Rockefeller University
- UCSF Helen Diller Family Comprehensive Cancer Center
- University of California
- University of California, San Francisco
- University of Pennsylvania
- Yale University