Browsing by Author "Singh, Parmit"
Now showing items 1-10 of 10
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Allosteric Integrase Inhibitor Influences on HIV-1 Integration and Roles of LEDGF/p75 and HDGFL2 Host Factors
Singh, Parmit; Li, Wen; Bedwell, Gregory J.; Fadel, Hind J.; Poeschla, Eric M.; Engelman, Alan N. (MDPI, 2022-08)Allosteric integrase (IN) inhibitors (ALLINIs), which are promising preclinical compounds that engage the lens epithelium-derived growth factor (LEDGF)/p75 binding site on IN, can inhibit different aspects of human ... -
CPSF6 LICENSES HIV-1 INTEGRATION INTO POL II-PAUSED GENES REGULATED by P-TEFb and U2 snRNP
Singh, Parmit; Annamalai, Arun; Kvaratskhelia, Mamuka; Engelman, Alan (2023-05)Pre-mRNA splicing regulates promoter-proximal Pol II pausing and alternative polyadenylation (APA). Splicing inhibitors increase pausing and use of proximal polyadenylation sites (PAS) for comparatively long (>4 introns) ... -
HIV-1 Integration Favors Genes Associated With Promoter-Proximal Pol II Pausing
Singh, Parmit; Annamalai, Arun; Kvaratkshelia, Mamuka; Engelman, Alan (2021-05)HIV-1 integration targeting is mediated by interactions of viral integrase and capsid with LEDGF/p75 and CPSF6, respectively. HIV-1 also prefers to integrate into highly spliced genes, but the role of pre-mRNA splicing in ... -
HIV-1 Preferentially Targets Genes Regulated by PAF-1 and U2 snRNP for Integration
Singh, Parmit; Annamalai, Arun; Kvaratkshelia, Mamuka; Engelman, Alan (2023-08-04)Pre-mRNA splicing is coupled with promoter-proximal Pol II pausing and alternative polyadenylation (APA). Splicing inhibitors increase pausing and the use of proximal polyadenylation sites (PAS) in intron rich genes by ... -
LEDGF/P75 DIRECTS HIV-1 TO INTEGRATE INTO HIGHLY SPLICED GENES DESPITE THEIR COMPARATIVELY LOW EXPRESSION
Singh, Parmit; Engelman, AlanIntegration of HIV-1 into genes depends on multiple factors including transcription, splicing, LEDGF/p75, and CPSF6. But, the precise role of mRNA splicing in HIV-1 integration targeting is unclear. Transcriptional intron ... -
LEDGF/p75-dependent HIV-1 integration targeting into spliced genes: A role for the DNA damage response
Singh, Parmit; Engelman, Alan (2020-04)HIV-1 integration site selection is regulated at the level of transcription, splicing, histone modifications, super enhancer, nuclear architecture, and interactions of viral proteins with host factors. However, the mechanism ... -
mRNA splicing targets HIV integration into PAF-1-regulated genes.
Singh, Parmit; Annamalai, Arun; Kvaratkshelia, Mamuka; Engelman, Alan (2024-03-01)Pre-mRNA co-transcriptional splicing is coupled with promoter-proximal Pol II pausing and alternative polyadenylation (APA)1,2. Splicing inhibitors increase pausing and the use of upstream or proximal polyadenylation sites ... -
Pre-mRNA Splicing and Gene Density are Significant Determinants of Lentiviral Integration
Singh, Parmit; Chivukula, Vidya; Cherepanov, Peter; Engelman, Alan (2021-05)Nuclear speckles harbor proteins important for transcription and pre-mRNA splicing. HIV-1 preintegration complexes localize to speckles in a capsid (CA)-CPSF6 dependent manner and preferentially target speckle-associated ... -
Spatial and Genomic Correlates of HIV-1 Integration Site Targeting
Singh, Parmit; Bedwell, Gregory; Engelman, Alan (MDPI AG, 2022-02-14)HIV-1 integrase and capsid proteins interact with host proteins to direct preintegration complexes to active transcription units within gene-dense regions of chromosomes for viral DNA integration. Analyses of spatially-derived ... -
Spotlighting Parmit Kumar Singh: a Q&A
Singh, Parmit (Harvard University Center for AIDS Research, 2022-04-01)