8id2

Publication Abstract from PubMed

The pre-spliceosomal complex involves interactions between U1 and U2 snRNPs, where a ubiquitin-like domain (ULD) of SF3A1, a component of U2 snRNP, binds to the stem-loop 4 (SL4; the UUCG tetraloop) of U1 snRNA in U1 snRNP. Here, we reported the 1.80 A crystal structure of human SF3A1 ULD (ULDSF3A1) complexed with SL4. The structural part of ULDSF3A1 (res. 704-785) adopts a typical beta-grasp fold with a topology of beta1-beta2-alpha1-310a-beta3-beta4-310b-beta5, closely resembling that of ubiquitin, except for the length and structure of the beta1/beta2 loop. A patch on the surface formed by three ULDSF3A1-specific residues, Lys756 (beta3), Phe763 (beta4) and Lys765 (following beta4), contacts the canonical UUCG tetraloop structure. In contrast, the directly following C-terminal tail composed of 786KERGGRKK793 was essentially stretched. The main or side chains of all the residues interacted with the major groove of the stem helix; the RGG residues adopted a peculiar conformation for RNA recognition. These findings were confirmed by mutational studies using bio-layer interferometry. Collectively, a unique combination of the beta-grasp fold and the C-terminal tail constituting ULDSF3A1 is required for the SL4-specific binding. This interaction mode also suggests that putative post-translational modifications, including ubiquitination in ULDSF3A1, directly inhibit SL4 binding.

Structural insights into recognition of SL4, the UUCG stem-loop, of human U1 snRNA by the ubiquitin-like domain, including the C-terminal tail in the SF3A1 subunit of U2 snRNP.,Nameki N, Terawaki SI, Takizawa M, Kitamura M, Muto Y, Kuwasako K J Biochem. 2023 Jul 31;174(2):203-216. doi: 10.1093/jb/mvad033. PMID:37094335^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.