YTHDC1 regulates distinct post-integration steps of HIV-1 replication and is important for viral infectivity View Full Text


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Article Info

DATE

2022-01-31

AUTHORS

Sarah N’Da Konan, Emmanuel Ségéral, Fabienne Bejjani, Maryam Bendoumou, Mélissa Ait Said, Sarah Gallois-Montbrun, Stéphane Emiliani

ABSTRACT

BackgroundThe recent discovery of the role of m6A methylation in the regulation of HIV-1 replication unveiled a novel layer of regulation for HIV gene expression. This epitranscriptomic modification of HIV-1 RNAs is under the dynamic control of specific writers and erasers. In addition, cytoplasmic readers of the m6A mark are recruited to the modified viral RNAs and regulate HIV-1 replication. Yet, little is known about the effects of m6A writers and readers on the biogenesis of HIV-1 RNAs.ResultsWe showed that the METTL3/14 m6A methyltransferase complex and the m6A YTHDF2 cytoplasmic writer down regulates the abundance of HIV-1 RNAs in infected cells. We also identified the m6A nuclear writer YTHDC1 as a novel regulator of HIV-1 transcripts. In HIV-1 producer cells, we showed that knocking down YTHDC1 increases the levels of unspliced and incompletely spliced HIV-1 RNAs, while levels of multiply spliced transcripts remained unaffected. In addition, we observed that depletion of YTHDC1 has no effect on the nuclear cytoplasmic distribution of viral transcripts. YTHDC1 binds specifically to HIV-1 transcripts in a METTL3-dependent manner. Knocking down YTHDC1 reduces the expression of Env and Vpu viral proteins in producer cells and leads to the incorporation of unprocessed Env gp160 in virus particles, resulting in the decrease of their infectivity.ConclusionsOur findings indicate that, by controlling HIV-1 RNA biogenesis and protein expression, the m6A nuclear reader YTHDC1 is required for efficient production of infectious viral particles.Graphical Abstract More... »

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4

References to SciGraph publications

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  • 2011-10-16. N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO in NATURE CHEMICAL BIOLOGY
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  • 2014-09-21. Structural basis for selective binding of m6A RNA by the YTHDC1 YTH domain in NATURE CHEMICAL BIOLOGY
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    http://scigraph.springernature.com/pub.10.1186/s12977-022-00589-1

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    36 Env
    37 Env gp160
    38 HIV gene expression
    39 HIV-1 RNA
    40 HIV-1 RNAs
    41 HIV-1 producer cells
    42 HIV-1 replication
    43 HIV-1 transcripts
    44 RNA
    45 RNA biogenesis
    46 RNAs
    47 ResultsWe
    48 YTHDC1
    49 abundance
    50 addition
    51 biogenesis
    52 cells
    53 complexes
    54 control
    55 cytoplasmic distribution
    56 decrease
    57 depletion
    58 discovery
    59 distribution
    60 dynamic control
    61 effect
    62 efficient production
    63 epitranscriptomic modifications
    64 erasers
    65 expression
    66 expression of env
    67 findings
    68 gene expression
    69 gp160
    70 incorporation
    71 infected cells
    72 infectious viral particles
    73 infectivity
    74 layer
    75 levels
    76 levels of multiply
    77 m6A marks
    78 m6A methylation
    79 m6A methyltransferase complex
    80 m6A writers
    81 manner
    82 marks
    83 methylation
    84 methyltransferase complex
    85 modification
    86 multiply
    87 novel layer
    88 novel regulator
    89 nuclear-cytoplasmic distribution
    90 particles
    91 post-integration steps
    92 producer cells
    93 production
    94 protein
    95 protein expression
    96 reader YTHDC1
    97 readers
    98 recent discovery
    99 regulation
    100 regulator
    101 replication
    102 role
    103 specific writers
    104 step
    105 transcripts
    106 viral RNA
    107 viral infectivity
    108 viral particles
    109 viral proteins
    110 viral transcripts
    111 virus particles
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