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Protein 61K, encoded by a gene (PRPF31) linked to autosomal dominant retinitis pigmentosa, is required for U4/U6*U5 tri-snRNP formation and pre-mRNA splicing.
EMBO J. 2002 Mar 01; 21(5):1148-57.EJ

Abstract

In each round of nuclear pre-mRNA splicing, the U4/U6*U5 tri-snRNP must be assembled from U4/U6 and U5 snRNPs, a reaction that is at present poorly understood. We have characterized a 61 kDa protein (61K) found in human U4/U6*U5 tri-snRNPs, which is homologous to yeast Prp31p, and show that it is required for this step. Immunodepletion of protein 61K from HeLa nuclear extracts inhibits tri-snRNP formation and subsequent spliceosome assembly and pre-mRNA splicing. Significantly, complementation with recombinant 61K protein restores each of these steps. Protein 61K is operationally defined as U4/U6 snRNP-specific as it remains bound to this particle at salt concentrations where the tri-snRNP dissociates. However, as shown by two-hybrid analysis and biochemical assays, protein 61K also interacts specifically with the U5 snRNP-associated 102K protein, indicating that it physically tethers U4/U6 to the U5 snRNP to yield the tri-snRNP. Interestingly, protein 61K is encoded by a gene (PRPF31) that has been shown to be linked to autosomal dominant retinitis pigmentosa. Thus, our studies suggest that disruptions in tri-snRNP formation and function resulting from mutations in the 61K protein may contribute to the manifestation of this disease.

Authors+Show Affiliations

Max Planck Institute for Biophysical Chemistry, Department of Cellular Biochemistry, Am Fassberg 11, D-37077 Göttingen, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11867543

Citation

Makarova, Olga V., et al. "Protein 61K, Encoded By a Gene (PRPF31) Linked to Autosomal Dominant Retinitis Pigmentosa, Is Required for U4/U6*U5 tri-snRNP Formation and pre-mRNA Splicing." The EMBO Journal, vol. 21, no. 5, 2002, pp. 1148-57.
Makarova OV, Makarov EM, Liu S, et al. Protein 61K, encoded by a gene (PRPF31) linked to autosomal dominant retinitis pigmentosa, is required for U4/U6*U5 tri-snRNP formation and pre-mRNA splicing. EMBO J. 2002;21(5):1148-57.
Makarova, O. V., Makarov, E. M., Liu, S., Vornlocher, H. P., & Lührmann, R. (2002). Protein 61K, encoded by a gene (PRPF31) linked to autosomal dominant retinitis pigmentosa, is required for U4/U6*U5 tri-snRNP formation and pre-mRNA splicing. The EMBO Journal, 21(5), 1148-57.
Makarova OV, et al. Protein 61K, Encoded By a Gene (PRPF31) Linked to Autosomal Dominant Retinitis Pigmentosa, Is Required for U4/U6*U5 tri-snRNP Formation and pre-mRNA Splicing. EMBO J. 2002 Mar 1;21(5):1148-57. PubMed PMID: 11867543.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protein 61K, encoded by a gene (PRPF31) linked to autosomal dominant retinitis pigmentosa, is required for U4/U6*U5 tri-snRNP formation and pre-mRNA splicing. AU - Makarova,Olga V, AU - Makarov,Evgeny M, AU - Liu,Sunbin, AU - Vornlocher,Hans-Peter, AU - Lührmann,Reinhard, PY - 2002/2/28/pubmed PY - 2002/5/15/medline PY - 2002/2/28/entrez SP - 1148 EP - 57 JF - The EMBO journal JO - EMBO J VL - 21 IS - 5 N2 - In each round of nuclear pre-mRNA splicing, the U4/U6*U5 tri-snRNP must be assembled from U4/U6 and U5 snRNPs, a reaction that is at present poorly understood. We have characterized a 61 kDa protein (61K) found in human U4/U6*U5 tri-snRNPs, which is homologous to yeast Prp31p, and show that it is required for this step. Immunodepletion of protein 61K from HeLa nuclear extracts inhibits tri-snRNP formation and subsequent spliceosome assembly and pre-mRNA splicing. Significantly, complementation with recombinant 61K protein restores each of these steps. Protein 61K is operationally defined as U4/U6 snRNP-specific as it remains bound to this particle at salt concentrations where the tri-snRNP dissociates. However, as shown by two-hybrid analysis and biochemical assays, protein 61K also interacts specifically with the U5 snRNP-associated 102K protein, indicating that it physically tethers U4/U6 to the U5 snRNP to yield the tri-snRNP. Interestingly, protein 61K is encoded by a gene (PRPF31) that has been shown to be linked to autosomal dominant retinitis pigmentosa. Thus, our studies suggest that disruptions in tri-snRNP formation and function resulting from mutations in the 61K protein may contribute to the manifestation of this disease. SN - 0261-4189 UR - https://www.unboundmedicine.com/medline/citation/11867543/Protein_61K_encoded_by_a_gene__PRPF31__linked_to_autosomal_dominant_retinitis_pigmentosa_is_required_for_U4/U6_U5_tri_snRNP_formation_and_pre_mRNA_splicing_ L2 - https://doi.org/10.1093/emboj/21.5.1148 DB - PRIME DP - Unbound Medicine ER -