Biology subjects

Anisimova, A. S.

Publications and source records attributed to Anisimova, A. S..

7 recordsLinked to original sources

bioRxiv2025

Ancestral P-body proteins rewired for autophagic recyclingin the early land plant Marchantia polymorpha

Processing bodies (P-bodies) are conserved ribonucleoprotein (RNP) granules central to RNA metabolism across eukaryotes. Although the mechanisms underlying their assembly are well understood, the pathways governing their selective turnover remain unclear. Here, we identify the conserved decapping proteins EDC4 and DCP1 as a selective autophagy receptor pair responsible for P-body turnover in the early land plant Marchantia polymorpha. MpEDC4 engages ATG8 via a canonical AIM motif, while MpDCP1 contains a previously unrecognized reverse AIM within its intrinsically disordered region. Mutations disrupting these motifs impair autophagic degradation of P-bodies, demonstrating a cooperative receptor mechanism. Notably, this autophagic function is lineage-specific, as orthologs in Arabidopsis and humans lack ATG8-binding capacity. Strikingly, heterologous expression of MpEDC4 in human cells promotes degradation of -synuclein, a protein strongly linked to Parkinsons disease etiology. Our findings thus uncover an evolutionary innovation that links RNA metabolism to selective autophagy and opens avenues for cross-kingdom engineering of targeted protein degradation pathways.

plant biology↗

bioRxiv2025

Dual regulation of the unfolded protein response by IGF2BP3 during ER stress

Misfolded protein accumulation in the endoplasmic reticulum (ER) perturbs cellular homeostasis, causing pathological ER stress. The Unfolded Protein Response (UPR) is a highly conserved signaling cascade that restores ER homeostasis by countering ER protein overload. Transcriptional response is paramount for UPR signaling and negating ER stress. While multiple UPR-linked mRNAs are post-transcriptionally regulated, the mechanisms mediating this regulation are unclear. Here, we demonstrate that the highly conserved RNA-binding protein IGF2BP3 interacts with transcripts encoding a subset of UPR effectors. During ER stress, IGF2BP3 destabilized many of these target transcripts, including UPR targets. In contrast, IGF2BP3 stabilized mRNAs encoding transcriptional regulators and thereby upregulated expression of UPR target genes. This dual regulation allows IGF2BP3 to differentially upregulate stress response genes while tuning down the expression of other transcripts during ER stress, relieving protein folding load during this critical response. Our data reveal that posttranscriptional mechanisms control transcription, thus forming gene regulatory networks that robustly tune the UPR.

cell biology↗

bioRxiv2025

The coordinated action of UFMylation and ribosome-associated quality control pathway clears arrested nascent chains at the endoplasmic reticulum

Clearance of incomplete nascent polypeptides resulting from ribosomal stalling is essential for protein homeostasis. While ribosome-associated quality control (RQC) mechanisms that degrade these polypeptides are well-characterized in the cytosol, how stalled endoplasmic reticulum (ER)-bound ribosomes are cleared remains poorly understood. Stalled ER-bound ribosomes are marked by ubiquitin-fold modifier 1 (UFM1) on large ribosomal subunit protein RPL26, but the precise function and regulation of this process are unclear. Here, we demonstrate that canonical RQC factors associate with ribosomes stalled at the ER. Functional cellular assays using ER-targeted stalling reporters reveal that while ribosome splitting is a prerequisite for UFMylation of RPL26, the UFMylation persists without late RQC components that are involved in the clearance of arrested nascent chains (NEMF and LTN1). The UFM1 E3 ligase complex binds to and UFMylates the 60S-peptidyl-tRNA complex and, in concert with the canonical RQC pathway, facilitates the clearance of arrested polypeptides. Our findings reveal that UFMylation acts to maintain translational integrity at the ER.

cell biology↗

bioRxiv2023

IGF2BP1 phosphorylation regulates ribonucleoprotein condensate formation by impairing low-affinity protein and RNA interactions

The insulin-like growth factor 2 mRNA binding protein (IGF2BP1) is a conserved RNA-binding protein that regulates RNA stability, localization, and translation. IGF2BP1 is part of various ribonucleoprotein (RNP) condensates regulating RNA outputs. However, the mechanism that regulates its assembly into condensates remains unknown. Here we found, using proteomics, that IGF2BP1 phosphorylation at S181 in a disordered linker is regulated in a stress-dependent manner. Phosphomimetic mutations in two disordered linkers, S181E and Y396E, modulated RNP condensate formation by IGF2BP1 without impacting its binding affinity for RNA. Intriguingly, the S181E mutant, which lies in linker 1, impaired IGF2BP1 condensate formation in vitro and in cells, whereas a Y396E mutant in the second linker increased condensate size and dynamics. Structural approaches showed that the first linker binds RNAs nonspecifically through its RGG/RG motif, an interaction weakened in the S181E mutant. Notably, linker 2 interacts with IGF2BP1s folded domains and these interactions were partially impaired in the Y396E mutant. Our data reveal how phosphorylation modulates low affinity interaction networks in disordered linkers to regulate RNP condensate formation.

biochemistry↗

bioRxiv2023

Human tissues exhibit diverse composition of translation machinery

While protein synthesis is vital for the majority of cell types of the human body, diversely differentiated cells require specific translation regulation. This suggests specialization of translation machinery across tissues and organs. Using transcriptomic data from GTEx, FANTOM, and Gene Atlas we systematically explored the abundance of transcripts encoding translation factors and aminoacyl-tRNA synthetases (ARSases) in human tissues. We revised a few known and identified several novel translation-related genes exhibiting strict tissue-specific expression. The proteins they encode include eEF1A1, eEF1A2, PABPC1L, PABPC3, eIF1B, eIF4E1B, eIF4ENIF1, and eIF5AL1. Furthermore, our analysis revealed a pervasive tissue-specific relative abundance of translation machinery components (e.g. PABP and eRF3 paralogs, eIF2B subunits, eIF5MPs, and some ARSases), suggesting presumptive variance in the composition of translation initiation, elongation, and termination complexes. These conclusions were largely confirmed by the analysis of proteomic data. Finally, we paid attention to sexual dimorphism in the repertoire of translation factors encoded in sex chromosomes (eIF1A, eIF2{gamma}, and DDX3), and identified testis and brain as organs with the most diverged expression of translation-associated genes.

molecular biology↗

bioRxiv2020

Multi-faceted deregulation of gene expression and protein synthesis with age

Protein synthesis represents a major metabolic activity of the cell. However, how it is affected by aging and how this in turn impacts cell function remains largely unexplored. To address this question, herein we characterized age-related changes in both the transcriptome and translatome of mouse tissues over the entire lifespan. Expression of the majority of differentially expressed genes followed a U-shaped curve with the turning point around 3-months-old. We showed that transcriptome changes govern changes in the translatome and are associated with altered expression of genes involved in inflammation, extracellular matrix and lipid metabolism. We also identified genes that may serve as candidate biomarkers of aging. At the translational level, we uncovered sustained down-regulation of a set of 5 terminal oligopyrimidine (5TOP) transcripts encoding protein synthesis and ribosome biogenesis machinery and regulated by the mTOR pathway. For many of them, ribosome occupancy dropped 3-fold or even more. Moreover, with age, ribosome coverage gradually decreased in the vicinity of start codons and increased near stop codons, revealing complex age-related changes in the translation process. Taken together, our results reveal systematic and multi-dimensional deregulation in protein synthesis, showing how this major cellular process declines with age.

systems biology↗

bioRxiv2018

The comparative and genetic methods for East European Unionidae taxonomy

Taxonomy of freshwater mussels from family Unionidae has been ambiguous for a long time. A number of methods used for their identification, including the so-called comparative method, are based on shell morphology. However, this morphology turned out to have a high level of within-species variation, and the shape of the shell of a specimen depends strongly on its environment and conditions of growth. For these reasons, the number of species recognized by the comparative method kept increasing. We applied both the comparative morphological method and methods of molecular genetics to address the taxonomy of Unionidae. We performed the comprehensive study of 70 specimens of Unionidae mussels collected from the River Ivitza, Volga basin. The specimens represented 14 comparative species, belonging to 4 comparative genera of Unionidae: Colletopterum, Pseudanodonta, Unio and Crassiana. Sequencing of the nuclear (ITS1) and mitochondrial (COI, 16S rDNA) genetic regions revealed 5 groups with high within-group genetic homogeneity separated from each other by long genetic distances. According to the comparison with the available sequences, these groups correspond to 3 Eastern European genera and 5 species: Anodonta anatina, Pseudanodonta complanata, Unio pictorum, Unio tumidus and Unio crassus. The results obtained indicate that the comparative method is inappropriate for the taxonomic analysis of East European Unionidae.

zoology↗