snoRNA-facilitated protein secretion revealed by transcriptome-wide snoRNA target identification

Bei Liu; Tong Wu; Bernadette A Miao; Fei Ji; Shun Liu; Pingluan Wang; Yutao Zhao; Yuhao Zhong; Arunkumar Sundaram; Tie-Bo Zeng; Marta Majcherska-Agrawal; Robert J Keenan; Tao Pan; Chuan He

doi:10.1016/j.cell.2024.10.046

snoRNA-facilitated protein secretion revealed by transcriptome-wide snoRNA target identification

Cell. 2024 Nov 21:S0092-8674(24)01269-8. doi: 10.1016/j.cell.2024.10.046. Online ahead of print.

Authors

Bei Liu¹, Tong Wu¹, Bernadette A Miao², Fei Ji³, Shun Liu¹, Pingluan Wang¹, Yutao Zhao¹, Yuhao Zhong¹, Arunkumar Sundaram⁴, Tie-Bo Zeng¹, Marta Majcherska-Agrawal⁵, Robert J Keenan⁴, Tao Pan⁶, Chuan He⁷

Affiliations

¹ Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA; Howard Hughes Medical Institute, Chicago, IL 60637, USA.
² Howard Hughes Medical Institute, Chicago, IL 60637, USA; Pritzker School of Molecular Engineering, The University of Chicago, Chicago, IL 60637, USA; Medical Scientist Training Program, The University of Chicago, Chicago, IL 60637, USA.
³ Howard Hughes Medical Institute, Chicago, IL 60637, USA; Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL 60637, USA; Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL 60637, USA.
⁴ Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA.
⁵ Howard Hughes Medical Institute, Chicago, IL 60637, USA; Committee on Genetics, Genomics & System Biology, The University of Chicago, Chicago, IL 60637, USA.
⁶ Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA. Electronic address: taopan@uchicago.edu.
⁷ Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA; Howard Hughes Medical Institute, Chicago, IL 60637, USA; Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA; Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA. Electronic address: chuanhe@uchicago.edu.

PMID: 39579764
DOI: 10.1016/j.cell.2024.10.046

Abstract

Small nucleolar RNAs (snoRNAs) are non-coding RNAs known for guiding RNA modifications, including 2'-O-methylation (N_m) and pseudouridine (Ψ). While snoRNAs may also interact with other RNAs, such as mRNA, the full repertoire of RNAs targeted by snoRNA remains elusive due to the lack of effective technologies that identify snoRNA targets transcriptome wide. Here, we develop a chemical crosslinking-based approach that comprehensively detects cellular RNA targets of snoRNAs, yielding thousands of previously unrecognized snoRNA-mRNA interactions in human cells and mouse brain tissues. Many interactions occur outside of snoRNA-guided RNA modification sites, hinting at non-canonical functions beyond RNA modification. We find that one of these snoRNAs, SNORA73, targets mRNAs that encode secretory proteins and membrane proteins. SNORA73 also interacts with 7SL RNA, part of the signal recognition particle (SRP) required for protein secretion. The mRNA-SNORA73-7SL RNA interactions enhance the association of the SNORA73-target mRNAs with SRP, thereby facilitating the secretion of encoded proteins.

Keywords: RNA modifications Ψ and N(m); protein secretion; protein translocation; snoRNA molecular glue; snoRNA-7SL RNA interaction; snoRNA-mRNA interaction.