PCID2, a subunit of the Drosophila TREX-2 nuclear export complex, is essential for both mRNA nuclear export and its subsequent cytoplasmic trafficking

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

“…In literature, PCID2 has been shown to regulate gene expression at multiple levels. The main role of PCID2 described in literature concerns co-transcriptional mRNA processing, and is linked to its function as part of the Transcription and Export Complex 2 (TREX2), that couples transcription with transport of mRNPs containing nascent RNA to the nuclear pore complex for its subsequent export to the cytoplasm [19][20][21][22][23] . Independent of its role as part of the TREX2 complex, PCID2 has been shown to have a role in genome and protein stability 24,25 , regulation of embryonic stem cell development and transcriptional regulation of specific genes in hematopoietic stem cells 27,28 .…”

“…PCID2 promotes HIV-1 latency by enforcing blocks at transcription initiation Of the functions currently described for PCID2, two stand out as particularly relevant for its role in HIV latency: first is its function in eukaryotic RNA metabolism in context of the TREX2 complex 19,20,22 , and second its distinct role in the transcriptional regulation of lymphoid lineage commitment genes 28 . Because PCID2 differentially binds the latent LTR, we first aimed to determine whether the presence of PCID2 at the HIV-1 promoter mediates its role in repressing HIV-1 gene expression at a transcriptional level.…”

“…Mammalian TREX2 complex is formed by the PCI-containing subunits MCM3AP, DSS1 and PCID2 that form the scaffold and RNA binding platform of the TREX2 complex and subunits ENY2 and CETN2/3,that form the nuclear pore binding dock. TREX2 is hence recruited to nascent RNA and facilitates export of mRNPs via the NXF1 pathway [19][20][21][22]41 . We first addressed to what extent viral RNA export is regulated by PCID2 and examined the distribution of intron-containing and completely spliced HIV-1 vRNA species in the nuclear and cytoplasmic compartments upon PCID2 depletion.…”

“…Catchet-MS also identified the host protein PCI domain containing 2 (PCID2) to be enriched at the HIV-1 promoter in the latent state. PCID2 (human homologue of yeast protein Thp1) is mainly described in literature as part of the multi-subunit Transcription and Export Complex 2 (TREX2), composed of PCID2, GANP, DSS1, ENY2 and CETN2/3 subunits, which links transcription with mRNA export by binding to nascent RNA containing messenger ribonucleoprotein (mRNP) complexes and mediating their transport from transcription sites to the nuclear pore for subsequent export [19][20][21][22][23] . Outside of the TREX2 complex, other functions have been ascribed to PCID2, including roles in genome instability and preventing R-Loop formation 24,25 , in protein stability 26,27 and transcription regulation of lymphoid commitment genes 28 .…”

PCID2 Subunit of the Drosophila TREX-2 Complex Has Two RNA-Binding Regions

“…Apart from playing a role in mRNA export, TREX-2 is involved in positioning genes in the nucleus, preventing genome instability, and regulating gene transcription [4,[8][9][10][11][12]. A knockdown of TREX-2 subunits distorts mRNA export and leads to mRNA accumulation in the cell nucleus [1,[3][4][5]9,[13][14][15]. The TREX-2 complex occurs in the nucleoplasm and at the periphery of the nucleus, colocalizing with the nuclear pore complex (NPC) [4,9,16,17].…”