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SUMO2 promotes histone pre-mRNA processing by stabilizing histone locus body interactions and facilitating U7 snRNP
Shuying He1, Pin Lyu2, Marnie W Skinner1
1Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.
Genes & Development
|July 10, 2025
Summary
Small ubiquitin-related modifier 2 (SUMO2) is crucial for proper histone mRNA processing. It ensures correct 3' end cleavage and prevents polyadenylation, maintaining histone protein balance.
Area of Science:
- Molecular Biology
- Cell Biology
- Gene Expression
Background:
- Histone mRNAs are unique nonpolyadenylated transcripts requiring specialized processing in the histone locus body (HLB).
- Dysregulation of histone mRNA processing, leading to polyadenylation, disrupts histone protein homeostasis and is linked to human diseases.
- The precise mechanisms of HLB assembly and U7 small nuclear ribonucleoprotein particle (snRNP) biogenesis remain incompletely understood.
Purpose of the Study:
- To investigate the novel functions of small ubiquitin-related modifier 2 (SUMO2) in histone pre-mRNA processing.
- To elucidate the role of SUMO2 in histone locus body (HLB) assembly and U7 snRNP biogenesis.
- To identify factors contributing to histone mRNA polyadenylation and its impact on cellular homeostasis.
Main Methods:
- Utilized a SUMO2 knockout osteosarcoma cell line to assess histone pre-mRNA processing.
- Analyzed histone mRNA polyadenylation levels and histone locus body (HLB) dynamics.
- Investigated the U7 snRNP complex levels and the role of Lsm11 and U7 snRNA in rescuing processing defects.
Main Results:
- SUMO2 deficiency resulted in impaired 3' end cleavage and global histone mRNA polyadenylation.
- SUMO2 knockout cells exhibited increased HLB dynamics and reduced U7 snRNP complex levels.
- Overexpression of Lsm11 and U7 snRNA rescued processing defects, and a SUMO-interacting motif in Lsm11 was identified as critical for U7 snRNP formation.
Conclusions:
- SUMO2 plays a critical role in promoting histone pre-mRNA 3' end processing.
- SUMO2 stabilizes histone locus body (HLB) interactions and facilitates U7 snRNP assembly, thereby preventing aberrant histone mRNA polyadenylation.
- These findings highlight SUMO2 as a key regulator of histone homeostasis and provide insights into HLB and U7 snRNP biogenesis.
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