Hari Krishna Yalamanchili
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View article: NUDT21 Regulates Macrophage Cytokine Responses via Alternative Polyadenylation in ARDS
NUDT21 Regulates Macrophage Cytokine Responses via Alternative Polyadenylation in ARDS Open
View article: Senolytic-Resistant Senescent Cells Have a Distinct SASP Profile and Functional Impact: The Path to Developing Senosensitizers
Senolytic-Resistant Senescent Cells Have a Distinct SASP Profile and Functional Impact: The Path to Developing Senosensitizers Open
The senescent cell (SC) fate is linked to aging, multiple disorders and diseases, and physical dysfunction. Senolytics, agents that selectively eliminate 30-70% of SCs, act by transiently disabling the senescent cell anti-apoptotic pathway…
View article: A protective role of SRC-1 against aging associated cognitive decline
A protective role of SRC-1 against aging associated cognitive decline Open
We identified a protective role of SRC1 against aging associated cognitive decline, potentially by promoting the expression of S100A6.
View article: HIV-1 Infection Regulates Gene Expression by Altering Alternative Polyadenylation Through CPSF6 and CPSF5 Delocalization
HIV-1 Infection Regulates Gene Expression by Altering Alternative Polyadenylation Through CPSF6 and CPSF5 Delocalization Open
HIV-1 viral core transport to the nucleus, an early infection event, triggers cleavage and polyadenylation specificity factor (CPSF)5 and CPSF6 to translocate from paraspeckles to nuclear speckles, forming puncta-like structures. CPSF5 and…
View article: Alpha-synuclein abundance and localization are regulated by the RNA-binding protein PUMILIO1
Alpha-synuclein abundance and localization are regulated by the RNA-binding protein PUMILIO1 Open
The protein α-synuclein, encoded by SNCA, accumulates in Parkinson's disease (PD) and other synucleinopathies for reasons that remain unclear. Here, we investigated whether SNCA is regulated in vivo by the RNA-binding protein PUM1. We esta…
View article: Effects of cannabinoid receptor-1 antagonist MRI-1867 on C5ar1 signaling in attenuating lung remodeling in mice induced with experimental arthritis
Effects of cannabinoid receptor-1 antagonist MRI-1867 on C5ar1 signaling in attenuating lung remodeling in mice induced with experimental arthritis Open
View article: Changes in the FXR-cistrome and alterations in bile acid physiology in Wilson disease
Changes in the FXR-cistrome and alterations in bile acid physiology in Wilson disease Open
Background: Wilson disease (WD) is an autosomal recessive disorder that results in excessive hepatic copper, causing hepatic steatosis, inflammation, fibrosis, cirrhosis, and liver failure. Previous studies have revealed dysregulation of m…
View article: Hyaluronidase-1 mediates postprandial suppression of hepatic gluconeogenesis
Hyaluronidase-1 mediates postprandial suppression of hepatic gluconeogenesis Open
Hepatic gluconeogenesis is a critical process that generates glucose from non-carbohydrate precursors during fasting to support vital organs like the brain and red blood cells. Postprandially, this process is rapidly suppressed to allow fo…
View article: Protocol for unlocking alternative polyadenylation insights from bulk RNA-seq data with PolyAMiner-Bulk
Protocol for unlocking alternative polyadenylation insights from bulk RNA-seq data with PolyAMiner-Bulk Open
PolyAMiner-Bulk, a deep-learning-based algorithm to decode alternative polyadenylation (APA) dynamics from bulk RNA sequencing (RNA-seq) data, enables scientists to identify and quantify APA events from processed bulk RNA-seq data. The pro…
View article: Acute MeCP2 loss in adult mice reveals transcriptional and chromatin changes that precede neurological dysfunction and inform pathogenesis
Acute MeCP2 loss in adult mice reveals transcriptional and chromatin changes that precede neurological dysfunction and inform pathogenesis Open
View article: The big tau splice isoform resists Alzheimer’s-related pathological changes
The big tau splice isoform resists Alzheimer’s-related pathological changes Open
SUMMARY In Alzheimer’s disease (AD), the microtubule-binding protein tau becomes abnormally hyperphosphorylated and aggregated in selective brain regions such as the cortex and hippocampus 1–3 . However, other brain regions like the cerebe…
View article: Histone proteoform analysis reveals epigenetic changes in adult mouse brown adipose tissue in response to cold stress
Histone proteoform analysis reveals epigenetic changes in adult mouse brown adipose tissue in response to cold stress Open
Background Regulation of the thermogenic response by brown adipose tissue (BAT) is an important component of energy homeostasis with implications for the treatment of obesity and diabetes. Our preliminary analyses of RNA-Seq data uncovered…
View article: A GREB1-steroid receptor feedforward mechanism governs differential GREB1 action in endometrial function and endometriosis
A GREB1-steroid receptor feedforward mechanism governs differential GREB1 action in endometrial function and endometriosis Open
View article: PolyAMiner-Bulk is a deep learning-based algorithm that decodes alternative polyadenylation dynamics from bulk RNA-seq data
PolyAMiner-Bulk is a deep learning-based algorithm that decodes alternative polyadenylation dynamics from bulk RNA-seq data Open
Alternative polyadenylation (APA) is a key post-transcriptional regulatory mechanism; yet, its regulation and impact on human diseases remain understudied. Existing bulk RNA sequencing (RNA-seq)-based APA methods predominantly rely on pred…
View article: <scp>MATR3</scp> pathogenic variants differentially impair its cryptic splicing repression function
<span>MATR3</span> pathogenic variants differentially impair its cryptic splicing repression function Open
Matrin‐3 (MATR3) is an RNA‐binding protein implicated in neurodegenerative and neurodevelopmental diseases. However, little is known regarding the role of MATR3 in cryptic splicing within the context of functional genes and how disease‐ass…
View article: CPSF3 inhibition blocks pancreatic cancer cell proliferation through disruption of core histone mRNA processing
CPSF3 inhibition blocks pancreatic cancer cell proliferation through disruption of core histone mRNA processing Open
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited effective treatment options, potentiating the importance of uncovering novel drug targets. Here, we target cleavage and polyadenylation specificity factor 3 (CPSF3), …
View article: Differential effects of MATR3 variants on its cryptic splicing repression function
Differential effects of MATR3 variants on its cryptic splicing repression function Open
MATR3 is an RNA-binding protein implicated in neurodegenerative and neurodevelopmental diseases. However, little is known regarding the role of MATR3 in cryptic splicing within the context of functional genes and how disease-associated var…
View article: Histone proteoform analysis reveals epigenetic changes in adult mouse brown adipose tissue in response to cold stress
Histone proteoform analysis reveals epigenetic changes in adult mouse brown adipose tissue in response to cold stress Open
Regulation of the thermogenic response by brown adipose tissue (BAT) is an important component of energy homeostasis with implications for the treatment of obesity and diabetes. Our preliminary analyses uncovered many nodes representing ep…
View article: SF3B1-dependent alternative splicing is critical for maintaining endometrial homeostasis and the establishment of pregnancy
SF3B1-dependent alternative splicing is critical for maintaining endometrial homeostasis and the establishment of pregnancy Open
The remarkable potential of human endometrium to undergo spontaneous remodeling is shaped by controlled spatiotemporal gene expression patterns. Although hormone-driven transcription shown to govern these patterns, the post-transcriptional…
View article: A Comprehensive and Integrative Approach to MeCP2 Disease Transcriptomics
A Comprehensive and Integrative Approach to MeCP2 Disease Transcriptomics Open
Mutations in MeCP2 result in a crippling neurological disease, but we lack a lucid picture of MeCP2′s molecular role. Individual transcriptomic studies yield inconsistent differentially expressed genes. To overcome these issues, we demonst…
View article: Alternative polyadenylation alters protein dosage by switching between intronic and 3′UTR sites
Alternative polyadenylation alters protein dosage by switching between intronic and 3′UTR sites Open
Alternative polyadenylation (APA) creates distinct transcripts from the same gene by cleaving the pre-mRNA at poly(A) sites that can lie within the 3′ untranslated region (3′UTR), introns, or exons. Most studies focus on APA within the 3′U…
View article: PolyAMiner-Bulk: A Machine Learning Based Bioinformatics Algorithm to Infer and Decode Alternative Polyadenylation Dynamics from bulk RNA-seq data
PolyAMiner-Bulk: A Machine Learning Based Bioinformatics Algorithm to Infer and Decode Alternative Polyadenylation Dynamics from bulk RNA-seq data Open
More than half of human genes exercise alternative polyadenylation (APA) and generate mRNA transcripts with varying 3’ untranslated regions (UTR). However, current computational approaches for identifying cleavage and polyadenylation sites…
View article: PGC-1α senses the CBC of pre-mRNA to dictate the fate of promoter-proximally paused RNAPII
PGC-1α senses the CBC of pre-mRNA to dictate the fate of promoter-proximally paused RNAPII Open
View article: Sex-specific epigenetic development in the mouse hypothalamic arcuate nucleus pinpoints human genomic regions associated with body mass index
Sex-specific epigenetic development in the mouse hypothalamic arcuate nucleus pinpoints human genomic regions associated with body mass index Open
Recent genome-wide association studies corroborate classical research on developmental programming indicating that obesity is primarily a neurodevelopmental disease strongly influenced by nutrition during critical ontogenic windows. Epigen…
View article: Sex-specific epigenetic development in the mouse hypothalamic arcuate nucleus pinpoints human genomic regions associated with body mass index
Sex-specific epigenetic development in the mouse hypothalamic arcuate nucleus pinpoints human genomic regions associated with body mass index Open
Obesity risk may be rooted in epigenetic development of the brain during early-life, potentially accounting for critical windows for exposure and sex disparities in risk. Analysis of whole-genome bisulfite sequencing (WGBS) and RNA-seq dat…
View article: Cleavage stimulating factor 64 depletion mitigates cardiac fibrosis through alternative polyadenylation
Cleavage stimulating factor 64 depletion mitigates cardiac fibrosis through alternative polyadenylation Open
View article: Disruption of MeCP2–TCF20 complex underlies distinct neurodevelopmental disorders
Disruption of MeCP2–TCF20 complex underlies distinct neurodevelopmental disorders Open
Significance Loss-of-function mutations in MECP2 cause the neurological disorder Rett syndrome (RTT), but the precise molecular mechanism driving pathogenesis remains unclear. Using an unbiased approach to identify proteins that interact w…
View article: MECP2pedia: A Comprehensive Transcriptome Portal for MECP2 Disease Research
MECP2pedia: A Comprehensive Transcriptome Portal for MECP2 Disease Research Open
Summary Mutations in MeCP2 result in a crippling neurological disease, but we lack a lucid picture of MeCP2s molecular role. Focusing on individual transcriptomic studies yields inconsistent differentially expressed genes. We have aggregat…
View article: Emerging roles of alternative cleavage and polyadenylation (APA) in human disease
Emerging roles of alternative cleavage and polyadenylation (APA) in human disease Open
In the messenger RNA (mRNA) maturation process, the 3′‐end of pre‐mRNA is cleaved and a poly(A) sequence is added, this is an important determinant of mRNA stability and its cellular functions. More than 60%–70% of human genes have three o…
View article: Dual targeting of brain region‐specific kinases potentiates neurological rescue in Spinocerebellar ataxia type 1
Dual targeting of brain region‐specific kinases potentiates neurological rescue in Spinocerebellar ataxia type 1 Open