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The autoantigen La protein is a conserved component of eukaryotic ribonucleoprotein complexes that binds the 3' poly(U) sequences of nascent RNA polymerase III transcripts to assist folding and maturation. This specific recognition is mediated by the N-terminal domain (NTD) of La, which comprises a La motif and an RNA recognition motif (RRM). Here, we report near complete H, C and N backbone and sidechain assignments for the RRM domain of La protein from Trypanosoma brucei.
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http://dx.doi.org/10.1007/s12104-020-09980-5 | DOI Listing |
Transcription and splicing are coupled both temporally and physically. A previous cryo-EM structure of the human U1 snRNP and RNA polymerase pol II complex has shown that U1 snRNP uses predominantly the RRM domain of U1-70K to directly interact with the RPB2 subunit of pol II. However, residues on U1-70K involved in the interaction with pol II are not conserved in yeast U1-70K, raising the question whether yeast U1 snRNP interacts with pol II in a similar manner.
View Article and Find Full Text PDFCurr Res Struct Biol
December 2025
Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology (IIT) Delhi, New Delhi, 110016, India.
The CRISPR/Cas system is a potential tool for genome editing, yet it faces challenges due to off-target activity caused by mismatches at specific positions. However, Off-target activity can be minimized by optimal design of guide RNA (gRNA) but there remains a possibility of unintended cleavage, highlighting the role of the Cas nuclease in off-target recognition and binding the target site. This study focuses on comparing the conformational dynamics and stability of Wildtype, RR, RVR, RRm and RVRm variants of AsCas12a with gRNA-DNA bound complexes.
View Article and Find Full Text PDFJ Am Chem Soc
August 2025
Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Biomolecular condensates enrich specific client molecules while excluding others, often modulating conformational landscapes, and hence functions, of molecules dissolved within them. NMR-based atomic resolution studies have focused on interactions between scaffold proteins and the unfolded states of client proteins to understand the factors that influence client partitioning into condensed phases. However, characterization of interactions involving the folded client conformer is required to obtain a complete picture of how dissolution within the condensed phase affects the client energy landscape.
View Article and Find Full Text PDFNucleic Acids Res
August 2025
Magnetic Resonance Center (CERM) and Department of Chemistry, University of Florence, and Consorzio Interuniversitario Risonanze Magnetiche di Metalloproteine (CIRMMP), Sesto Fiorentino 50019, FI, Italy.
The Human Musashi-1 (MSI-1) is an RNA-binding protein that recognizes (G/A)U1-3AGU and UAG sequences in diverse RNAs through two RNA Recognition Motif (RRM) domains and regulates the fate of target RNA. Here, we have combined structural biology and computational approaches to analyse the binding of the RRM domains of human MSI-1 with single-stranded and structured RNA ligands. We have used our recently developed computational tool RRMScorer to design a set of substitutions in the MSI-1 protein and the investigated RNA strands to modulate the binding affinity and selectivity.
View Article and Find Full Text PDFEur J Cancer
September 2025
Department of Oncology, Mayo Clinic, Rochester, MN, United States. Electronic address:
Purpose: Neoadjuvant ± adjuvant immunotherapy improves event-free survival (EFS) versus adjuvant immunotherapy alone for high-risk resectable Stage III melanoma. However, the optimal regimen balancing efficacy and tolerability is unknown. T-cell immunoglobulin and ITIM domain (TIGIT) is a promising immune checkpoint whose therapeutic potential in Stage III melanoma is underexplored.
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