Universität zu Köln

Ajamian, Lara, Abel, Karen, Rao, Shringar, Vyboh, Kishanda, Garcia-de-Gracia, Francisco, Soto-Rifo, Ricardo, Kulozik, Andreas E., Gehring, Niels H. ORCID: 0000-0001-7792-1164 and Mouland, Andrew J. (2015). HIV-1 Recruits UPF1 but Excludes UPF2 to Promote Nucleocytoplasmic Export of the Genomic RNA. Biomolecules, 5 (4). S. 2808 - 2840. BASEL: MDPI. ISSN 2218-273X

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Abstract

Unspliced, genomic HIV-1 RNA (vRNA) is a component of several ribonucleoprotein complexes (RNP) during the viral replication cycle. In earlier work, we demonstrated that the host upframeshift protein 1 (UPF1), a key factor in nonsense-mediated mRNA decay (NMD), colocalized and associated to the viral structural protein Gag during viral egress. In this work, we demonstrate a new function for UPF1 in the regulation of vRNA nuclear export. We establish that the nucleocytoplasmic shuttling of UPF1 is required for this function and demonstrate that UPF1 exists in two essential viral RNPs during the late phase of HIV-1 replication: the first, in a nuclear export RNP that contains Rev, CRM1, DDX3 and the nucleoporin p62, and the second, which excludes these nuclear export markers but contains Gag in the cytoplasm. Interestingly, we observed that both UPF2 and the long isoform of UPF3a, UPF3aL, but not the shorter isoforms UPF3aS and UPF3b, are excluded from the UPF1-Rev-CRM1-DDX3 complex as they are negative regulators of vRNA nuclear export. Insilico protein-protein docking analyses suggest that Rev binds UPF1 in a region that overlaps the UPF2 binding site, thus explaining the exclusion of this negative regulatory factor by HIV-1 that is necessary for vRNA trafficking. This work uncovers a novel and unique regulatory circuit involving several UPF proteins that ultimately regulate vRNA nuclear export and trafficking.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ajamian, Lara UNSPECIFIED UNSPECIFIED UNSPECIFIED Abel, Karen UNSPECIFIED UNSPECIFIED UNSPECIFIED Rao, Shringar UNSPECIFIED UNSPECIFIED UNSPECIFIED Vyboh, Kishanda UNSPECIFIED UNSPECIFIED UNSPECIFIED Garcia-de-Gracia, Francisco UNSPECIFIED UNSPECIFIED UNSPECIFIED Soto-Rifo, Ricardo UNSPECIFIED UNSPECIFIED UNSPECIFIED Kulozik, Andreas E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gehring, Niels H. UNSPECIFIED orcid.org/0000-0001-7792-1164 UNSPECIFIED Mouland, Andrew J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-384822
DOI:	10.3390/biom5042808
Journal or Publication Title:	Biomolecules
Volume:	5
Number:	4
Page Range:	S. 2808 - 2840
Date:	2015
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2218-273X
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language HUMAN-IMMUNODEFICIENCY-VIRUS; EXON-JUNCTION COMPLEX; MESSENGER-RNA; NUCLEAR EXPORT; CRYSTAL-STRUCTURE; GENE-EXPRESSION; REV FUNCTION; NMD FACTORS; PROTEIN; DECAY Multiple languages Biochemistry & Molecular Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/38482