HIV-1 splicing is controlled by local RNA structure and binding of splicing regulatory proteins at the major 5′ splice site | Zendy

Nancy Müeller | Zendy; Ben Berkhout | Zendy; Atze T. Das | Zendy

Open Access

HIV-1 splicing is controlled by local RNA structure and binding of splicing regulatory proteins at the major 5′ splice site

Author(s) -

Nancy Müeller,

Ben Berkhout,

Atze T. Das

Publication year - 2015

Publication title -

journal of general virology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.55

H-Index - 167

eISSN - 1465-2099

pISSN - 0022-1317

DOI - 10.1099/vir.0.000122

Subject(s) - rna splicing , biology , sr protein , rna , exonic splicing enhancer , rna binding protein , genetics , intron , splicing factor , splice site mutation , alternative splicing , nucleic acid secondary structure , computational biology , messenger rna , gene

The 5' leader region of the human immunodeficiency virus 1 (HIV-1) RNA genome contains the major 5' splice site (ss) that is used in the production of the many spliced viral RNAs. This splice-donor (SD) region can fold into a stable stem-loop structure and the thermodynamic stability of this RNA hairpin influences splicing efficiency. In addition, splicing may be modulated by binding of splicing regulatory (SR) proteins, in particular SF2/ASF (SRSF1), SC35 (SRSF2), SRp40 (SRSF5) and SRp55 (SRSF6), to sequence elements in the SD region. The role of RNA structure and SR protein binding in splicing control was previously studied by functional analysis of mutant SD sequences. The interpretation of these studies was complicated by the fact that most mutations simultaneously affect both structure and sequence elements. We therefore tried to disentangle the contribution of these two variables by designing more precise SD region mutants with a single effect on either the sequence or the structure. The current analysis indicates that HIV-1 splicing at the major 5'ss is modulated by both the stability of the local RNA structure and the binding of splicing regulatory proteins.

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