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Kadumuri, R. V.

Publications and source records attributed to Kadumuri, R. V..

4 recordsLinked to original sources

Transcription termination safeguards quiescent chromatin for faithful cell-cycle re-entry

Quiescence is a conserved program of endurance and readiness in non-cycling cells that is fundamental to the longevity of eukaryotic lineages, from clonal microbial populations to human regenerative tissues. While this G0 state is universally associated with a compact chromatin organization, the active safeguards that preserve this structural template--and their necessity for future division competence and fidelity--remain unknown. Here we show, using fission yeast as a model, that chromatin structural maintenance in quiescence requires the enforcement of transcription termination by the conserved factor Ppn1PNUTS/Ref2. We identify a minimal disordered region in Ppn1 that resolves a physical conflict in the quiescent genome by preventing the transcriptional "eviction" of cohesin. Loss of this safeguard drives a progressive structural erosion that deregulates cyclin-dependent kinase (CDK) dynamics and causes lethal aneuploidy upon cell-cycle re-entry. Notably, this deterioration is not an inevitable terminal state; re-establishing termination via a brief Ppn1 pulse resets division fidelity by stabilizing a core de novo cohesin landscape. These findings redefine quiescent chromatin as an actively maintainable blueprint rather than a passive standby state established at G0 entry. We propose that "quiescence exhaustion" is driven by transcriptional stress eroding genomic organization, defining a structural limit to cellular longevity.

genetics↗

Molecular attributes of intrinsically disordered regions in secretomes influence fungal pathogenesis

Secretory proteins are crucial for establishing fungal infection through biomolecular interactions with the host. Accumulating evidence suggest that intrinsically disordered regions (IDRs) in proteins facilitate molecular interactions. How do IDRs of secretory proteins influence fungal pathogenesis? By analyzing 195,359 secretory proteins of 73 fungal species, we find that IDRs in plant pathogen extracellular non-effectors are enriched for weak polyampholytes and polyelectrolytes. These could adopt beads-on-string conformation effectively promoting assembly of diverse enzymes aiding swift degradation of host cell wall. Both animal pathogen secretory proteins and intracellular plant pathogen effectors show enrichment for strong polyampholytes, potentially aiding phase-separation and organizing intracellular biological matter to hijack or suppress host machinery. Importantly, IDRs of plant pathogen effectors which mimic host IDRs could have emerged through convergent evolution, while those of non-effectors might have evolved de novo. Thus, specific molecular attributes of fungal secretome IDRs can influence initiation, establishment and long-term persistence of infection.

systems biology↗

ERF transcription factor regulons underpin growth-defence trade-off under acute heat stress in rice seedlings

O_LIRice, a staple cereal crop, faces significant threats from rising temperatures, affecting all growth stages including early seedling establishment. Despite being critical in determining overall growth and productivity, response to heat stress during the early seedling stage remains understudied. This research aimed to assess the impact of acute heat stress on rice seedlings and unravel underlying molecular mechanisms. C_LIO_LIRice seedlings were exposed to varying intensities and durations of heat stress to determine a critical threshold affecting growth. To elucidate the transcription factor (TF)-mediated regulatory mechanisms and their functional interactome in response to stress, transcriptomic analysis of shoots and roots exposed to acute heat stress was performed. C_LIO_LITranscriptome analysis unveiled a comprehensive TF-target regulatory map for shoots and roots, potentially involved in the modulation of growth-defence trade-off in response to acute heat stress. Ethylene Responsive Factors (ERFs) emerged as central regulators, with phytohormones ethylene and jasmonic acid acting as upstream modulators. Pre-treatment with these phytohormones alleviated the adverse effects of heat stress. C_LIO_LIThis study uncovers key molecular mechanisms governing rice seedling responses to acute heat stress involving ERFs-hormonal interactions. Modulating these core regulators presents a promising strategy to enhance heat resilience, addressing global food security amid rising temperatures. C_LI

plant biology↗

Amino acid repeat signatures underlying human-pathogen interactions

Emerging evidence suggests that amino acid homorepeats (HRs) in proteins (HRPs) contribute to protein interactability. What is the role of HRs in human-pathogen protein interactions? We find that pathogens engage physiologically important human HRPs, thereby affecting diverse host physiological processes. From the pathogen standpoint, (i) eukaryotic pathogens engage more HRPs but with host-sparse HRs, leading to disparate and discriminate interactions, (ii) prokaryotic pathogens engage less HRPs but with host-abundant non-polar HRs via host protein proxies bringing about discriminate or promiscuous interactions and (iii) viral pathogens engage more HRPs with host-abundant polar uncharged HRs affecting promiscuous interactions using host-partner HR tract mimicry. To propel further research, we introduce a resource Hi-PHI (http://hiphi.iisertirupati.ac.in/) cataloging critical information about human and pathogen HRPs and HRs. We propose mechanisms to (i) repurpose drugs targeting human HRPs engaged by pathogens for treating different infections and (ii) exploit HRs and their flanks as targets for pathogen-targeted anti-infectives.

systems biology↗