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Functional Interaction between U1snRNP and Sam68 Insures Proper 3' End Pre-mRNA Processing during Germ Cell
Chiara Naro1, Livia Pellegrini2, Ariane Jolly3
1Institute of Human Anatomy and Cell Biology, Catholic University of the Sacred Hearth, 00168 Rome, Italy; IRCCS Fondazione Santa Lucia, 00143 Rome, Italy.
Cell Reports
|March 14, 2019
Summary
The splicing regulator Sam68 controls extensive alternative last exon (ALE) splicing in male germ cells. This process is essential for male fertility, involving cooperation with U1snRNP to ensure proper transcript processing.
Area of Science:
- Molecular Biology
- Reproductive Biology
- Genetics
Background:
- Male germ cells exhibit remarkable transcriptomic diversity.
- Factors driving this diversity, particularly during meiosis, remain largely unknown.
- The splicing regulator Sam68 is crucial for spermatogenesis but its regulatory mechanisms are unclear.
Purpose of the Study:
- To investigate the role of Sam68 in regulating transcript diversity during male meiosis.
- To elucidate the mechanisms by which Sam68 controls gene expression in germ cells.
- To understand the functional implications of Sam68-mediated splicing for male fertility.
Main Methods:
- Analysis of splicing patterns in Sam68-deficient (Sam68-/-) germ cells.
- Identification of alternative last exon (ALE) regulation.
- Biochemical assays to assess physical interactions between Sam68 and U1snRNP.
- Assessment of U1snRNP recruitment to target sites.
Main Results:
- Sam68 operates an extensive splicing program in meiosis, focusing on ALE regulation.
- Loss of Sam68 leads to premature transcript termination at polyadenylation sites.
- Sam68-regulated ALEs involve proximity of U1snRNP and Sam68 binding motifs.
- Sam68 physically associates with U1snRNP, and its recruitment is impaired in Sam68-/- germ cells.
Conclusions:
- Sam68 and U1snRNP cooperate to ensure proper transcript processing during male meiosis.
- This interaction is critical for regulating alternative last exons and maintaining male fertility.
- The study reveals a novel mechanism for transcriptomic diversity essential for spermatogenesis.