TY - JOUR T1 - SR proteins and hnRNP H regulate the splicing of the HIV-1 tev-specific exon 6D. AU - Caputi,Massimo, AU - Zahler,Alan M, PY - 2002/2/16/pubmed PY - 2002/4/20/medline PY - 2002/2/16/entrez SP - 845 EP - 55 JF - The EMBO journal JO - EMBO J VL - 21 IS - 4 N2 - A naturally arising point mutation in the env gene of HIV-1 activates the aberrant inclusion of the cryptic exon 6D into most viral messages, leading to inefficient viral replication. We set out to understand how a single nucleotide substitution could cause such a dramatic change in splicing. We have determined that the exon 6D mutation promotes binding of the SR protein SC35 to the exon. Mutant exon 6D sequences function as a splicing enhancer when inserted into an enhancer-dependent splicing construct. hnRNP H family proteins bind to the enhancer as well; their binding is dependent on the sequence GGGA located just downstream of the point mutation and depletion-- reconstitution studies show that hnRNP H is essential for enhancer activity. A polypurine sequence located further downstream in exon 6D binds SR proteins but acts as an exonic splicing silencer. hnRNP H is required for interaction of U1 snRNP with the enhancer, independent of the point mutation. We propose that SC35 binding to the point mutation region may convert the hnRNP H-U1 snRNP complex into a splicing enhancer. SN - 0261-4189 UR - https://www.unboundmedicine.com/medline/citation/11847131/SR_proteins_and_hnRNP_H_regulate_the_splicing_of_the_HIV_1_tev_specific_exon_6D_ L2 - https://doi.org/10.1093/emboj/21.4.845 DB - PRIME DP - Unbound Medicine ER -