Identification of conserved, primary sequence motifs that direct retrovirus RNA fate

Nucleic Acids Research
Gatikrushna SinghKathleen Boris-Lawrie

Abstract

Precise stoichiometry of genome-length transcripts and alternatively spliced mRNAs is a hallmark of retroviruses. We discovered short, guanosine and adenosine sequence motifs in the 5'untranslated region of several retroviruses and ascertained the reasons for their conservation using a representative lentivirus and genetically simpler retrovirus. We conducted site-directed mutagenesis of the GA-motifs in HIV molecular clones and observed steep replication delays in T-cells. Quantitative RNA analyses demonstrate the GA-motifs are necessary to retain unspliced viral transcripts from alternative splicing. Mutagenesis of the GA-motifs in a C-type retrovirus validate the similar downregulation of unspliced transcripts and virion structural protein. The evidence from cell-based co-precipitation studies shows the GA-motifs in the 5'untranslated region confer binding by SFPQ/PSF, a protein co-regulated with T-cell activation. Diminished SFPQ/PSF or mutation of either GA-motif attenuates the replication of HIV. The interaction of SFPQ/PSF with both GA-motifs is crucial for maintaining the stoichiometry of the viral transcripts and does not affect packaging of HIV RNA. Our results demonstrate the conserved GA-motifs direct the fate of re...Continue Reading

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Citations

Jul 11, 2020·Proceedings of the National Academy of Sciences of the United States of America·Pengfei DingMichael F Summers
Apr 22, 2020·The Journal of Biological Chemistry·Gatikrushna SinghKathleen Boris-Lawrie
Oct 3, 2020·Viruses·Patrick S OsmerKathleen Boris-Lawrie
May 14, 2021·Microbiology and Molecular Biology Reviews : MMBR·Maelig G MorvanJay A Levy

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Methods Mentioned

BETA
PCR
enzyme-linked immunosorbent assay
electrophoretic mobility shift
ELISA
ELISAs
co-immunoprecipitation
electrophoresis
electrophoretic
immunoprecipitation
gel-filtration

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