Biology subjects

Thind, A.

Publications and source records attributed to Thind, A..

6 recordsLinked to original sources

bioRxiv2026

An RNA-centric atlas of human cell cycle regulation

Cell cycle progression is orchestrated by protein networks coordinating cell growth and division, yet the role of RNA-mediated mechanisms remains underexplored. Here, we define an RNA-centric landscape of human cell cycle control using palbociclib-synchronised normal diploid cells, profiling long non-coding RNAs (lncRNAs), transposable elements (TEs), alternative splicing (AS), and RNA-binding proteins (RBPs). We identify 104 cell cycle-regulated lncRNAs and validate lncRNA ENSG00000230615, whose perturbation alters cell cycle progression and downregulates neighbouring KLF17. Across the transcriptome, 297 TE loci exhibit differential expression dynamics during the cell cycle, with Alu elements upregulated during the G1-to-S transition. Cell-cycle-dependent AS changes affect 598 genes, with alternative 5' splice sites showing the largest shift in usage at the G1-to-S transition. Furthermore, we show that cytokinesis proteins act as non-canonical RBPs with RNA-dependent stability. This study provides a comprehensive resource on RNA-based cell cycle control and highlights an underappreciated layer of regulation mediated by RNA mechanisms.

cell biology↗

bioRxiv2025

An AGO2 adaptor expands the functional and evolutionary reach of microRNA targeting

Current models of microRNA (miRNA) silencing posit that RNA-sequence rules are sufficient for canonical targeting of mRNAs by Argonaute 2 (AGO2), the central protein of the miRNA-induced silencing complex (miRISC). Using chimeric eCLIP in CRISPR-edited LIMD1+/+, LIMD1+/-, and LIMD1-/- human small airway epithelial cells (hSAECs), we reveal a transcriptome-wide dependency on LIMD1, an AGO2 adaptor, for effective miRNA targeting and repression. In LIMD1-deficient cells, miRNA loading is uncoupled from productive targeting: despite increased AGO2-miRNA interactions, complexes engage fewer transcripts and sites, reducing occupancy and more than halving both the breadth and depth of targeting. We also observe altered AGO2 positional footprints across targets in LIMD1-deficient cells. LIMD1 dependence is most pronounced at defined RNA contexts: weak (GC-poor) seed pairings, interactions involving evolutionarily young miRNAs or sites that nonetheless form thermodynamically stable duplexes, with these losses particularly enriched in coding sequences of rapidly evolving C2H2-zinc-finger genes. Even within canonical seed repertoires of individual AGO2-miRNAs, LIMD1 is most critical at poorly conserved sites, indicating that LIMD1 broadens miRNA regulation beyond ancient, deeply conserved targets. In culture, LIMD1 deficiency de-represses oncogenic proteins that, in vivo, inversely correlate with LIMD1 levels in normal lung and adenocarcinoma, where LIMD1 is characteristically reduced, and whose dysregulation predicts poor survival. Thus, LIMD1 emerges as a key determinant of miRISC architecture, targeting, and potency, challenging RNA-centric models of miRNA function and exemplifying how adaptor proteins diversify post-transcriptional regulation. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=180 HEIGHT=200 SRC="FIGDIR/small/680889v2_ufig1.gif" ALT="Figure 1"> View larger version (58K): org.highwire.dtl.DTLVardef@e0f4f5org.highwire.dtl.DTLVardef@f23fd9org.highwire.dtl.DTLVardef@3de3f2org.highwire.dtl.DTLVardef@1404af2_HPS_FORMAT_FIGEXP M_FIG LIMD1 defines the scope of miRNA-mediated targeting and repression O_LIAGO2-chimeric eCLIP in CRISPR-edited human small airway epithelial cells (hSAECs) shows LIMD1 is required for productive AGO2-miRNA engagement transcriptome-wide. C_LIO_LILIMD1 deficiency reduces the AGO2-miRNA:targetome. Each AGO2-miRNA binds fewer targets, with lower occupancy per site and per transcript and fewer global silencing events. C_LIO_LILIMD1 dependence is strongest for GC-poor seed-sites, less conserved miRNAs and sites, and thermodynamically stronger duplexes. C_LIO_LIDosage-dependent effects of LIMD1 deficiency are broadly observed. C_LIO_LITarget-mRNA decay and translational repression are reduced in LIMD1-deficient hSAECs, increasing protein output. C_LIO_LIIn vivo, LIMD1 LOH-associated deficiency is prevalent and typically clonal in NSCLC. LIMD1 expression inversely correlates with oncogene levels in normal lung and adenocarcinoma, and target dysregulation predicts poor survival. C_LI C_FIG

molecular biology↗

bioRxiv2025

The RNA-binding protein RSRC2 promotes mitotic fidelity by interacting with the lncRNA C1QTNF1-AS1

Mitotic fidelity depends on proper chromosome alignment at the spindle equator, a process known as chromosome congression, driven by well-established protein networks. Whereas RNA-binding proteins and noncoding RNAs have been implicated in cell division, their interplay during this process remains unknown. Here, we discover that RSRC2, an arginine/serine-rich RNA-binding protein, plays an essential role in cell division by interacting with the long non-coding RNA C1QTNF1-AS1. The loss of either RSRC2 or C1QTNF1-AS1 results in defects in chromosome congression and mitotic progression. We show that RSRC2 interacts with distinct sets of proteins involved in splicing and centrosome biogenesis, contributing to the fidelity of cell division through two different mechanisms: one linked to the splicing of mitotic regulators and the other by localising to mitotic centrosomes for which the interaction with the C1QTNF1-AS1 RNA is required. Our study uncovers RSRC2 as a new regulator of cell division and illustrates how RNA-protein complexes promote error-free mitosis.

cell biology↗

bioRxiv2024

Putative neofunctionalization of a Poales-specific EXO70 clade

EXO70s are uniquely expanded in land plants compared to all other eukaryotic lineages. The functional implications of this expansion and diversification on the conserved role of EXO70 as a subunit of the octameric exocyst complex have remained unresolved. We previously demonstrated barley (Hordeum vulgare) EXO70FX12, a member of the monocot-specific EXO70FX clade, is required for resistance to wheat stripe rust in conjunction with the leucine-rich repeat receptor kinase (LRR-RK) HvPUR1. Through phylogenetic analysis, we identified unique features of the EXO70FX clade, leading us to hypothesize that this clade experienced neofunctionalization. Using structural predictions and protein-protein interaction assays, we demonstrate that HvEXO70FX12 lost the ability to serve as a subunit within the exocyst complex. We predict that the EXO70FX clade has largely lost exocyst association and represents a novel acquisition that emerged during Poales diversification for immunity.

plant biology↗

bioRxiv2021

A lineage-specific Exo70 is required for receptor kinase-mediated immunity in barley

In the evolution of land plants, the plant immune system has experienced expansion in immune receptor and signaling pathways. Lineage-specific expansions have been observed in diverse gene families that are potentially involved in immunity, but lack causal association. Here, we show that Rps8-mediated resistance in barley to the fungal pathogen Puccinia striiformis f. sp. tritici (wheat stripe rust) is conferred by a genetic module: LRR-RK and Exo70FX12, which are together necessary and sufficient. The Rps8 LRR-RK is the ortholog of rice extracellular immune receptor Xa21 and Exo70FX12 is a member of the Poales-specific Exo70FX clade. The Exo70FX clade emerged after the divergence of the Bromeliaceae and Poaceae, and comprises from 2 to 75 members in sequenced grasses. These results demonstrate the requirement of a lineage-specific Exo70FX12 in Rps8 LRR-RK immunity and suggest that the Exo70FX clade may have evolved a specialized role in receptor kinase signaling.

plant biology↗

bioRxiv2019

The proline synthesis enzyme P5CS forms cytoophidia in Drosophila

Compartmentation of enzymes via filamentation has arisen as a mechanism for the regulation of metabolism. In 2010, three groups independently reported that CTP synthase (CTPS) can assemble into a filamentous structure termed the cytoophidium. In searching for CTPS-interacting proteins, here we perform a yeast two-hybrid screening of Drosophila proteins and identify a putative CTPS-interacting protein, {Delta}1-pyrroline-5-carboxylate synthase (P5CS). Using Drosophila follicle cell as the in vivo model, we confirm that P5CS forms cytoophidia, which are associated with CTPS cytoophidia. Overexpression of P5CS increases the length of CTPS cytoophidia. Conversely, filamentation of CTPS affects the morphology of P5CS cytoophidia. Finally, in vitro analyses confirm the filament-forming property of P5CS. Our work links CTPS with P5CS, two enzymes involved in the rate-limiting steps in pyrimidine and proline biosynthesis, respectively.

cell biology↗