The secondary structure of the human immunodeficiency virus type 1 transcript modulates viral splicing and infectivity.
Splicing of human immunodeficiency virus type 1 (HIV-1) exon 6D is regulated by the presence of a complex splicing regulatory element (SRE) sequence that interacts with the splicing factors hnRNP H and SC35. In this work, we show that, in the context of the wild-type viral sequence, hnRNP H acts as a repressor of exon 6D inclusion independent of its binding to the SRE. However, hnRNP H binding to the SRE acts as an enhancer of exon 6D inclusion in the presence of a critical T-to-C mutation. These seemingly contrasting functional properties of hnRNP H appear to be caused by a change in the RNA secondary structure induced by the T-to-C mutation that affects the spatial location of bound hnRNP H with respect to the exon 6D splicing determinants. We propose a new regulatory mechanism mediated by RNA folding that may also explain the dual properties of hnRNP H in splicing regulation.
Basic Science Department, Florida Atlantic University, Boca Raton, Florida 33431, USA.
Joseph A
JA
Jablonski
Emanuele
E
Buratti
Cristiana
C
Stuani
Massimo
M
Caputi
D017398:Alternative Splicing; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D005091:Exons; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H / Q000737:chemistry*; D006801:Humans; D009154:Mutation; D009690:Nucleic Acid Conformation; D010957:Plasmids / Q000378:metabolism; D017433:Protein Structure, Secondary; D012313:RNA / Q000737:chemistry*; D012326:RNA Splicing; D034741:RNA, Small Interfering / Q000378:metabolism
D034541:Heterogeneous-Nuclear Ribonucleoprotein Group F-H; D034741:RNA, Small Interfering; D012313:RNA