@article{e21da0e757f549ffadf4f020f9b0cfd1,
title = "RBM33 directs the nuclear export of transcripts containing GC-rich elements",
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 = "GC content, GC-rich elements, NORAD, RBM33, lncRNAs, long noncoding RNAs, nuclear export",
author = "Anu Thomas and Frederick Rehfeld and He Zhang and Chang, {Tsung Cheng} and Mohammad Goodarzi and Frank Gillet and Mendell, {Joshua T.}",
note = "Funding Information: We thank John Doench, Bo Huang, Rudolf Jaenisch, David Root, David Sabatini, and Feng Zhang for plasmids; Vanessa Schmid, Rachel Bruce, and Caitlin Eaton in the McDermott Center Next-Generation Sequencing Core for assistance with high-throughput sequencing; Angie Mobley and the University of Texas Southwestern Flow Cytometry Core facility for assistance with FACS; Andrew Lemoff and the University of Texas Southwestern Proteomics Core facility for assistance with mass spectrometry; and Kathryn O{\textquoteright}Donnell and members of the Mendell laboratory for helpful comments on the manuscript. This work was supported by grants from the National Institutes of Health (R35CA197311 to J.T.M.), Cancer Prevention and Research Institute of Texas (RP220309 to J.T.M.), and the Welch Foundation (I-1961-20210327 to J.T.M.). J.T.M. is an investigator of the Howard Hughes Medical Institute (HHMI). This article is subject to HHMI{\textquoteright}s Open Access to Publications policy. HHMI laboratory heads have previously granted a nonexclusive CC BY 4.0 license to the public and a sublicensable license to HHMI in their research articles. Pursuant to those licenses, the author-accepted manuscript of this article can be made freely available under a CC BY 4.0 license immediately upon publication. Funding Information: We thank John Doench, Bo Huang, Rudolf Jaenisch, David Root, David Sabatini, and Feng Zhang for plasmids; Vanessa Schmid, Rachel Bruce, and Caitlin Eaton in the McDermott Center Next-Generation Sequencing Core for assistance with high-throughput sequencing; Angie Mobley and the University of Texas Southwestern Flow Cytometry Core facility for assistance with FACS; Andrew Lemoff and the University of Texas South-western Proteomics Core facility for assistance with mass spectrometry; and Kathryn O{\textquoteright}Donnell and members of the Mendell laboratory for helpful comments on the manuscript. This work was supported by grants from the National Institutes of Health (R35CA197311 to J.T.M.), Cancer Prevention and Research Institute of Texas (RP220309 to J.T.M.), and the Welch Foundation (I-1961-20210327 to J.T.M.). J.T.M. is an investigator of the Howard Hughes Medical Institute (HHMI). This article is subject to HHMI{\textquoteright}s Open Access to Publications policy. HHMI laboratory heads have previously granted a nonexclusive CC BY 4.0 license to the public and a sublicensable license to HHMI in their research articles. Pursuant to those licenses, the author-accepted manuscript of this article can be made freely available under a CC BY 4.0 license immediately upon publication. Publisher Copyright: {\textcopyright} 2022 Thomas et al.",
year = "2022",
month = may,
day = "1",
doi = "10.1101/GAD.349456.122",
language = "English (US)",
volume = "36",
pages = "550--565",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "9-10",
}