snRNA maturation in Saccharomyces cerevisie
Cell Biology
Final Report Abstract
Spliceosomes are important to excise intron sequences from pre-mRNA, which ensures proper protein expression. While the surveillance mechanisms for mRNAs are well-characterized, the quality control processes for non-coding RNAs (ncRNAs) remain less understood. Unlike mRNA, where guard proteins monitor maturation by allowing proper transcripts to exit the nucleus or targeting faulty ones for degradation, ncRNA surveillance systems are not fully elucidated. This study focuses on the maturation of the spliceosomal U6 snRNA, a transcript synthesized by RNA polymerase III, and uncovers both known and a novel quality control factor involved in its processing. It demonstrates that U6 snRNA is monitored by established guard proteins alongside a newly identified factor, Lhp1 (the human La protein), which ensures the correct loading of the Lsm ring in the nucleus, an essential step for its function. Once properly loaded, Mex67 binds to pre-U6, facilitating its export from the nucleus to the cytoplasm. In the cytoplasm, pre-U6 associates with Prp24, a protein that promotes annealing with pre-U4, an essential step in snRNP assembly. Any defects in di-snRNP formation are detected by guard proteins such as Npl3, Gbp2, and Hrb1, which remain bound to faulty pre-U6, preventing its re-import into the nucleus. Instead, these proteins recruit the decapping enzymes Dcp1 and Dcp2, leading to removal of the 5’ cap, and the exonuclease Xrn1, which degrades the defective RNA. Correctly assembled U4/U6 complexes are on the other hand released from the guard proteins and imported back into the nucleus for further maturation. This guard protein-mediated quality control system prevents faulty di-snRNPs from disrupting spliceosome function, emphasizing the importance of compartmentalized maturation and surveillance of ncRNAs. The findings also suggest that similar quality control mechanisms extend beyond coding RNAs, regard RNA polymerase II and III transcripts, involving comparable proteins and pathways, highlighting the broader significance of RNA surveillance in maintaining cellular RNA integrity.
Publications
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Initial spliceosomal U4/U6 di-snRNA formation occurs in the cytoplasm of Saccharomyces cerevisiae and requires a guard protein mediated quality control. Nucleic Acids Research, 54(1).
Wang, Xiaoxiao; Guo, Jian; Li, Jing & Krebber, Heike
