RBM33 directs the nuclear export of transcripts containing GC-rich elements
Open Access
- 19 May 2022
- journal article
- research article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 36 (9-10), 550-565
- https://doi.org/10.1101/gad.349456.122
Abstract
Although splicing is a major driver of RNA nuclear export, many intronless RNAs are efficiently exported to the cytoplasm through poorly characterized mechanisms. For example, GC-rich sequences promote nuclear export in a splicing-independent manner, but how GC content is recognized and coupled to nuclear export is unknown. Here, we developed a genome-wide screening strategy to investigate the mechanism of export of NORAD, an intronless cytoplasmic long noncoding RNA (lncRNA). This screen revealed an RNA binding protein, RBM33, that directs the nuclear export of NORAD and numerous other transcripts. RBM33 directly binds substrate transcripts and recruits components of the TREX–NXF1/NXT1 RNA export pathway. Interestingly, high GC content emerged as the feature that specifies RBM33-dependent nuclear export. Accordingly, RBM33 directly binds GC-rich elements in target transcripts. These results provide a broadly applicable strategy for the genetic dissection of nuclear export mechanisms and reveal a long-sought nuclear export pathway for transcripts with GC-rich sequences.Keywords
Funding Information
- McDermott Center Next-Generation Sequencing Core
- National Institutes of Health (R35CA197311)
- Cancer Prevention and Research Institute of Texas (RP220309)
- Welch Foundation (I-1961-20210327)
This publication has 63 references indexed in Scilit:
- The Cellular EJC Interactome Reveals Higher-Order mRNP Structure and an EJC-SR Protein NexusCell, 2012
- STAR: ultrafast universal RNA-seq alignerBioinformatics, 2012
- TREX exposes the RNA-binding domain of Nxf1 to enable mRNA exportNature Communications, 2012
- Export and stability of naturally intronless mRNAs require specific coding region sequences and the TREX mRNA export complexProceedings of the National Academy of Sciences of the United States of America, 2011
- PUF proteins: repression, activation and mRNA localizationTrends in Cell Biology, 2011
- Distinct Patterns of Expression and Evolution of Intronless and Intron-Containing Mammalian GenesMolecular Biology and Evolution, 2010
- UIF, a New mRNA Export Adaptor that Works Together with REF/ALY, Requires FACT for Recruitment to mRNACurrent Biology, 2009
- Adaptor Aly and co-adaptor Thoc5 function in the Tap-p15-mediated nuclear export of HSP70 mRNAThe EMBO Journal, 2009
- Mutually exclusive interactions drive handover of mRNA from export adaptors to TAPProceedings of the National Academy of Sciences of the United States of America, 2008
- Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profilesProceedings of the National Academy of Sciences of the United States of America, 2005