6ppn
Structure of S. pombe Lsm2-8 with unprocessed U6 snRNAStructure of S. pombe Lsm2-8 with unprocessed U6 snRNA
Structural highlights
Function[LSM6_SCHPO] Component of LSm protein complexes, which are involved in RNA processing and may function in a chaperone-like manner, facilitating the efficient association of RNA processing factors with their substrates. Component of the cytoplasmic LSM1-LSM7 complex, which is thought to be involved in mRNA degradation by activating the decapping step in the 5'-to-3' mRNA decay pathway. Component of the nuclear LSM2-LSM8 complex, which is involved in splicing of nuclear mRNAs. LSM2-LSM8 associates with multiple snRNP complexes containing the U6 snRNA (U4/U6 di-snRNP, spliceosomal U4/U6.U5 tri-snRNP, and free U6 snRNP). It binds directly to the 3'-terminal U-tract of U6 snRNA and plays a role in the biogenesis and stability of the U6 snRNP and U4/U6 snRNP complexes. LSM2-LSM8 probably also is involved degradation of nuclear pre-mRNA by targeting them for decapping, and in processing of pre-tRNAs, pre-rRNAs and U3 snoRNA (By similarity). [LSM3_SCHPO] Binds specifically to the 3'-terminal U-tract of U6 snRNA. [LSM7_SCHPO] Component of LSm protein complexes, which are involved in RNA processing and may function in a chaperone-like manner. Probable component of the spliceosome. [LSM2_SCHPO] Binds specifically to the 3'-terminal U-tract of U6 snRNA. [LSM8_SCHPO] Probable component of the spliceosome. [LSM4_SCHPO] Binds specifically to the 3'-terminal U-tract of U6 snRNA. [LSM5_SCHPO] Component of LSm protein complexes, which are involved in RNA processing and may function in a chaperone-like manner. LSm5 is required for processing of pre-tRNAs, pre-rRNAs and U3 snoRNA (By similarity). Publication Abstract from PubMedEukaryotes possess eight highly conserved Lsm (like Sm) proteins that assemble into circular, heteroheptameric complexes, bind RNA, and direct a diverse range of biological processes. Among the many essential functions of Lsm proteins, the cytoplasmic Lsm1-7 complex initiates mRNA decay, while the nuclear Lsm2-8 complex acts as a chaperone for U6 spliceosomal RNA. It has been unclear how these complexes perform their distinct functions while differing by only one out of seven subunits. Here, we elucidate the molecular basis for Lsm-RNA recognition and present four high-resolution structures of Lsm complexes bound to RNAs. The structures of Lsm2-8 bound to RNA identify the unique 2',3' cyclic phosphate end of U6 as a prime determinant of specificity. In contrast, the Lsm1-7 complex strongly discriminates against cyclic phosphates and tightly binds to oligouridylate tracts with terminal purines. Lsm5 uniquely recognizes purine bases, explaining its divergent sequence relative to other Lsm subunits. Lsm1-7 loads onto RNA from the 3' end and removal of the Lsm1 C-terminal region allows Lsm1-7 to scan along RNA, suggesting a gated mechanism for accessing internal binding sites. These data reveal the molecular basis for RNA binding by Lsm proteins, a fundamental step in the formation of molecular assemblies that are central to eukaryotic mRNA metabolism. Molecular basis for the distinct cellular functions of the Lsm1-7 and Lsm2-8 complexes.,Montemayor EJ, Virta JM, Hayes SM, Nomura Y, Brow DA, Butcher SE RNA. 2020 Jun 9. pii: rna.075879.120. doi: 10.1261/rna.075879.120. PMID:32518066[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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