The lncRNA NRON modulates HIV-1 replication in a NFAT-dependent manner and is differentially regulated by early and late viral proteins.
A majority of the human genome is transcribed into noncoding RNAs, of which the functions of long noncoding RNAs (lncRNAs) are poorly understood. Many host proteins and RNAs have been characterized for their roles in HIV/AIDS pathogenesis, but there is only one lncRNA, NEAT1, which is shown to affect the HIV-1 life cycle. We profiled 90 disease-related lncRNAs and found NRON (noncoding repressor of Nuclear Factor of Activated T cells [NFAT]) to be one of several lncRNAs whose expression was significantly altered following HIV-1 infection. The regulation of NRON expression during the HIV-1 life cycle was complex; its levels were reduced by the early viral accessory protein Nef and increased by the late protein Vpu. Consequently, Nef and Vpu also modulated activity of the transcription factor NFAT. The knockdown of NRON enhanced HIV-1 replication through increased activity of NFAT and the viral LTR. Using siRNA-mediated NFAT knockdown, we show the effects of NRON on HIV-1 replication to be mediated by NFAT, and the viral Nef and Vpu proteins to modulate NFAT activity through their effects on NRON. These findings add the lncRNA, NRON to the vast repertoire of host factors utilized by HIV for infection and persistence.
Virology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
Hasan
H
Imam
Virology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
Aalia Shahr
AS
Bano
Virology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
Paresh
P
Patel
Virology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
Prasida
P
Holla
Virology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
Shahid
S
Jameel
D057809:HEK293 Cells; D015658:HIV Infections / Q000235:genetics / Q000821:virology; D016325:HIV Long Terminal Repeat / Q000235:genetics; D015497:HIV-1 / Q000502:physiology*; D054298:Human Immunodeficiency Virus Proteins / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008954:Models, Biological; D050778:NFATC Transcription Factors / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000378:metabolism*; D054334:Viral Regulatory and Accessory Proteins / Q000378:metabolism*; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*; D000086082:Viroporin Proteins
D054298:Human Immunodeficiency Virus Proteins; D050778:NFATC Transcription Factors; D062085:RNA, Long Noncoding; D054334:Viral Regulatory and Accessory Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; C000603410:NRON long noncoding RNA, human; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins