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From Proteopedia
Cryo-EM structure of the spliceosomal U4/U6.U5 tri-snRNP
Structural highlights
Function[RSMB_YEAST] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. [LSM5_YEAST] Component of LSm protein complexes, which are involved in RNA processing and may function in a chaperone-like manner. Component of the cytoplasmic LSM1-LSM7 complex which is thought to be involved in mRNA degradation by activating the decapping step. 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 snRNP, U4/U6.U5 snRNP, and free U6 snRNP). It binds directly to the U6 snRNA and plays a role in the biogenesis and stability of the U6 snRNP and U4/U6 snRNP complexes. It probably also is involved degradation of nuclear pre-mRNA by targeting them for decapping. LSM5 binds specifically to the 3'-terminal U-tract of U6 snRNA. LSM2-LSM8 probably is involved in processing of pre-tRNAs, pre-rRNAs and U3 snoRNA. LSM5, probably in a complex that contains LSM2-LSM7 but not LSM1 or LSM8, associates with the precursor of the RNA component of RNase P (pre-P RNA) and may be involved in maturing pre-P RNA. LSM5 is required for processing of pre-tRNAs, pre-rRNAs and U3 snoRNA.[1] [2] [3] [4] [5] [SNU13_YEAST] Common component of the spliceosome and rRNA processing machinery. In association with the spliceosomal U4/U6.U5 tri-snRNP particle, required for splicing of pre-mRNA. In association with box C/D snoRNPs, required for processing of pre-ribosomal RNA (rRNA) and site-specific 2'-O-methylation of substrate RNAs. Essential for the accumulation and stability of U4 snRNA, U6 snRNA, and box C/D snoRNAs.[6] [7] [8] [LSM8_YEAST] 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 snRNP, spliceosomal U4/U6.U5 snRNP, and free U6 snRNP). It binds directly to the U6 snRNA and plays a role in the biogenesis and stability of the U6 snRNP and U4/U6 snRNP complexes. It probably also is involved degradation of nuclear pre-mRNA by targeting them for decapping. LSM2-LSM8 probably is involved in processing of pre-tRNAs, pre-rRNAs and U3 snoRNA. LSM2 is required for processing of pre-tRNAs, pre-rRNAs and U3 snoRNA.[9] [10] [11] [PRP4_YEAST] Involved in RNA splicing. Is required for the association of U4/U6 snRNP with U5 snRNP in an early step of spliceosome assembly. [LSM7_YEAST] Component of LSm protein complexes, which are involved in RNA processing and may function in a chaperone-like manner. Component of the cytoplasmic LSM1-LSM7 complex which is thought to be involved in mRNA degradation by activating the decapping step. 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 snRNP, spliceosomal U4/U6.U5 snRNP, and free U6 snRNP). It binds directly to the U6 snRNA and plays a role in the biogenesis and stability of the U6 snRNP and U4/U6 snRNP complexes. It probably also is involved degradation of nuclear pre-mRNA by targeting them for decapping. LSM7 binds specifically to the 3'-terminal U-tract of U6 snRNA. LSM2-LSM8 probably is involved in processing of pre-tRNAs, pre-rRNAs and U3 snoRNA. LSM7, probably in a complex that contains LSM2-LSM7 but not LSM1 or LSM8, associates with the precursor of the RNA component of RNase P (pre-P RNA) and may be involved in maturing pre-P RNA.[12] [13] [14] [PRP8_YEAST] Required for pre-spliceosome formation, which is the first step of pre-mRNA splicing. This protein is associated with snRNP U5. Has a role in branch site-3' splice site selection. Associates with the branch site-3' splice 3'-exon region. Also has a role in cell cycle.[15] [16] [17] [18] [LSM2_YEAST] Component of LSm protein complexes, which are involved in RNA processing and may function in a chaperone-like manner. Component of the cytoplasmic LSM1-LSM7 complex which is thought to be involved in mRNA degradation by activating the decapping step. 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 snRNP, U4/U6.U5 snRNP, and free U6 snRNP). It binds directly to the U6 snRNA and plays a role in the biogenesis and stability of the U6 snRNP and U4/U6 snRNP complexes. It probably also is involved degradation of nuclear pre-mRNA by targeting them for decapping. LSM2 binds specifically to the 3'-terminal U-tract of U6 snRNA. LSM2-LSM8 probably is involved in processing of pre-tRNAs, pre-rRNAs and U3 snoRNA. LSM2, probably in a complex that contains LSM2-LSM7 but not LSM1 or LSM8, associates with the precursor of the RNA component of RNase P (pre-P RNA) and may be involved in maturing pre-P RNA. LSM2 is required for processing of pre-tRNAs, pre-rRNAs and U3 snoRNA.[19] [20] [21] [22] [23] [LSM4_YEAST] Component of LSm protein complexes, which are involved in RNA processing and may function in a chaperone-like manner. Component of the cytoplasmic LSM1-LSM7 complex which is thought to be involved in mRNA degradation by activating the decapping step. Component of the nuclear LSM2-LSM8 complex, which is involved in splicing of nuclear mRNAs. LSM2-LSM8 associates with multiple spliceosome snRNP complexes containing the U6 snRNA (U4/U6 snRNP, U4/U6.U5 snRNP, and free U6 snRNP). It binds directly to the U6 snRNA and plays a role in the biogenesis and stability of the U6 snRNP and U4/U6 snRNP complexes. It probably also is involved degradation of nuclear pre-mRNA by targeting them for decapping. LSM4 binds specifically to the 3'-terminal U-tract of U6 snRNA. LSM2-LSM8 probably is involved in processing of pre-tRNAs, pre-rRNAs and U3 snoRNA. LSM4, probably in a complex that contains LSM2-LSM7 but not LSM1 or LSM8, associates with the precursor of the RNA component of RNase P (pre-P RNA) and may be involved in maturing pre-P RNA. LSM4 is required for processing of pre-tRNAs, pre-rRNAs and U3 snoRNA.[24] [25] [26] [27] [28] [RUXG_YEAST] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. [SMD2_YEAST] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. [DIB1_YEAST] Essential role in pre-mRNA splicing. Also essential for entry into mitosis (G2/M progression) as well as for chromosome segregation during mitosis. [PRP31_YEAST] Promotes the association of the U4/U6.U5 tri-snRNP particle with pre-spliceosomes to form the mature spliceosomal complex.[29] [BRR2_YEAST] RNA helicase that plays an essential role in pre-mRNA splicing as component of the U5 snRNP and U4/U6-U5 tri-snRNP complexes. Involved in spliceosome assembly, activation and disassembly. Mediates changes in the dynamic network of RNA-RNA interactions in the spliceosome. Catalyzes the ATP-dependent unwinding of U4/U6 RNA duplices, an essential step in the assembly of a catalytically active spliceosome.[30] [31] [32] [33] [SMD1_YEAST] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. Also binds telomerase RNA and is required for its accumulation.[34] [35] [LSM6_YEAST] 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. In association with PAT1, LSM1-LSM7 binds directly to RNAs near the 3'-end and prefers oligoadenylated RNAs over polyadenylated RNAs. 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. Component of a nucleolar LSM2-LSM7 complex, which associates with the precursor of the RNA component of RNase P (pre-P RNA) and with the small nucleolar RNA (snoRNA) snR5. It may play a role in the maturation of a subset of nucleolus-associated small RNAs.[36] [37] [38] [39] [RUXE_YEAST] Involved in pre-mRNA splicing. Binds and is required for the stability of snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. Involved in cap modification.[40] [RUXF_YEAST] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. [SN114_YEAST] Component of the U5 snRNP complex required for pre-mRNA splicing. Binds GTP. [PRP6_YEAST] Participates in pre-mRNA splicing. Part of the U4/U5/U6 tri-snRNP complex, one of the building blocks of the spliceosome. [LSM3_YEAST] Component of LSm protein complexes, which are involved in RNA processing and may function in a chaperone-like manner. Component of the cytoplasmic LSM1-LSM7 complex which is thought to be involved in mRNA degradation by activating the decapping step. 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 snRNP, U4/U6.U5 snRNP, and free U6 snRNP). It binds directly to the U6 snRNA and plays a role in the biogenesis and stability of the U6 snRNP and U4/U6 snRNP complexes. It probably also is involved degradation of nuclear pre-mRNA by targeting them for decapping. LSM3 binds specifically to the 3'-terminal U-tract of U6 snRNA. LSM2-LSM8 probably is involved in processing of pre-tRNAs, pre-rRNAs and U3 snoRNA. LSM3, probably in a complex that contains LSM2-LSM7 but not LSM1 or LSM8, associates with the precursor of the RNA component of RNase P (pre-P RNA) and may be involved in maturing pre-P RNA. LSM3 is required for processing of pre-tRNAs, pre-rRNAs and U3 snoRNA.[41] [42] [43] [44] [45] [46] [SMD3_YEAST] Involved in pre-mRNA splicing. Binds snRNA U1, U2, U4 and U5 which contain a highly conserved structural motif called the Sm binding site. Also binds telomerase RNA and is required for its accumulation.[47] [48] [PRP3_YEAST] Participates in pre-mRNA splicing. Part of the U4/U5/U6 tri-snRNP complex, one of the building blocks of the spliceosome.[49] Publication Abstract from PubMedSplicing of precursor messenger RNA is accomplished by a dynamic megacomplex known as the spliceosome. Assembly of a functional spliceosome requires a preassembled U4/U6.U5 tri-snRNP complex, which comprises the U5 small nuclear ribonucleoprotein (snRNP), the U4 and U6 small nuclear RNA (snRNA) duplex, and a number of protein factors. Here we report the three-dimensional structure of a Saccharomyces cerevisiae U4/U6.U5 tri-snRNP at an overall resolution of 3.8 angstroms by single-particle electron cryomicroscopy. The local resolution for the core regions of the tri-snRNP reaches 3.0 to 3.5 angstroms, allowing construction of a refined atomic model. Our structure contains U5 snRNA, the extensively base-paired U4/U6 snRNA, and 30 proteins including Prp8 and Snu114, which amount to 8495 amino acids and 263 nucleotides with a combined molecular mass of ~1 megadalton. The catalytic nucleotide U80 from U6 snRNA exists in an inactive conformation, stabilized by its base-pairing interactions with U4 snRNA and protected by Prp3. Pre-messenger RNA is bound in the tri-snRNP through base-pairing interactions with U6 snRNA and loop I of U5 snRNA. This structure, together with that of the spliceosome, reveals the molecular choreography of the snRNAs in the activation process of the spliceosomal ribozyme. The 3.8 A structure of the U4/U6.U5 tri-snRNP: Insights into spliceosome assembly and catalysis.,Wan R, Yan C, Bai R, Wang L, Huang M, Wong CC, Shi Y Science. 2016 Jan 29;351(6272):466-75. doi: 10.1126/science.aad6466. Epub 2016, Jan 7. PMID:26743623[50] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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