Dataset Information

PCID2 regulates HIV-1 transcription and viral RNA processing during latency

ABSTRACT: HIV-1 latency results from a combination of tightly regulated molecular processes that act at distinct steps of HIV-1 gene expression. In an effort to elucidate the molecular players that govern viral latency, we previously performed a dCas9 chromatin immunoprecipitation coupled with mass spectrometry (Catchet-MS) and identified proteins bound differentially to the latent LTR that putatively promote HIV-1 latency. Here we characterize the Catchet-MS identified PCI domain-containing 2 (PCID2) protein to play a dual role in promoting HIV-1 latency by enforcing both HIV-1 transcription repression as well as post-transcriptional blocks. PCID2 bound the latent HIV-1 LTR and repressed transcription initiation during latency. Depletion of PCID2 remodeled the chromatin landscape at the HIV-1 promoter and resulted in transcriptional activation and reversal of latency. Immunoprecipitation coupled to Mass Spectrometry identified the PCID2 interacting proteins to include members of the spliceosome and other splicing regulators, including negative regulators of viral RNA alternative splicing. PCID2 depletion resulted in over-splicing of intron-containing HIV-1 RNA and mis-regulated expression of vRNA splice variants. Finally, consistent with its role in NXF1-mediated nascent RNA nucleocytoplasmic export as part of the TREX2 complex, PCID2 modulates export of completely spliced vRNA. In summary, we demonstrate that PCID2 is a previously unidentified factor involved in HIV-1 latency regulation which plays a dual role in blocking HIV-1 gene expression by acting on transcription initiation as well as viral RNA processing.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Leukocyte

SUBMITTER: Jeroen Demmers

LAB HEAD: Jeroen Demmers

PROVIDER: PXD043334 | Pride | 2024-06-16

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	2434_L_RaquelCrespo_03OCT22_plusIRT_DDA_Control.raw	Raw
	2434_L_RaquelCrespo_03OCT22_plusIRT_DDA_PCID2_Flag2x.raw	Raw
	2434_L_RaquelCrespo_03OCT22_plusIRT_DIA_Control.raw	Raw
	2434_L_RaquelCrespo_03OCT22_plusIRT_DIA_PCID2_Flag2x.raw	Raw
	2434_parameters.txt	Txt

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Publications

PCID2 dysregulates transcription and viral RNA processing to promote HIV-1 latency.

Crespo Raquel R Ne Enrico E Reinders Julian J Meier Jenny I J JIJ Li Chengcheng C Jansen Sanne S Górska Alicja A Koçer Selin S Kan Tsung Wai TW Doff Wouter W Dekkers Dick D Demmers Jeroen J Palstra Robert-Jan RJ Rao Shringar S Mahmoudi Tokameh T

iScience 20240206 3

HIV-1 latency results from tightly regulated molecular processes that act at distinct steps of HIV-1 gene expression. Here, we characterize PCI domain-containing 2 (PCID2) protein, a subunit of the transcription and export complex 2 (TREX2) complex, to enforce transcriptional repression and post-transcriptional blocks to HIV-1 gene expression during latency. PCID2 bound the latent HIV-1 LTR (long terminal repeat) and repressed transcription initiation during latency. Depletion of PCID2 remodeled ...[more]

PMID: 38384833

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