Molecular cellJul 15, 2026

SMD2 recognizes RNA modifications to control mRNA processing and support tumor growth

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jul 16, 2026

Abstract

SMD2, a core spliceosomal component, is identified as a direct reader of pseudouridines (ψ) in mRNA.

SMD2 preferentially binds to ψ-modified RNA over unmodified uridines in human cells.
It collaborates with pseudouridine synthase family enzymes to regulate alternative splicing.
SMD2 recognizes ψ residues near exon-intron junctions to influence splicing outcomes.
The gene encoding SMD2, SNRPD2, is overexpressed in multiple cancers.
SMD2 is essential for tumor cell proliferation by modulating mRNA maturation.

Simplified

Pseudouridines (ψ) in mRNA are linked to alternative splicing, but their regulatory mechanisms remain unclear due to the lack of known reader proteins. Here, we identify SMD2, a core spliceosomal component, as a direct ψ reader. Through in vitro and ex vivo assays, we show that SMD2 preferentially binds to ψ-modified RNA over unmodified uridines in human cells. Specifically, SMD2 collaborates with ψ synthase (PUS) family enzymes to regulate alternative splicing by recognizing ψ residues near exon-intron junctions. Notably, SNRPD2, the gene encoding SMD2, is overexpressed in multiple cancers and is essential for tumor cell proliferation through modulating mRNA maturation. These findings establish a direct mechanistic link between ψ and spliceosomal function, which positions SMD2 as a key regulator of ψ-mediated splicing and a promising therapeutic target in cancer.

Full Text

Full text is available at the source.

View Full Text ↗

Funding

Competing interests

0%of authors

0 of 9

authors report competing interests

9 report none

PubMed

SMD2 recognizes RNA modifications to control mRNA processing and support tumor growth

Abstract

Full Text

Funding

Competing interests

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the mrna technology brief