Biology subjects

Guminska, N.

Publications and source records attributed to Guminska, N..

4 recordsLinked to original sources

bioRxiv2024

Efficient globin production during terminal erythropoiesis depends on the synergistic action of TENT5C poly(A) polymerase and LARP4/5

Red blood cell development is a unique process where reduced transcriptome and proteome complexity facilitates vast hemoglobin production. Here, we describe the cooperative role of cytoplasmic poly(A) polymerase TENT5C and the poly(A) tail-protecting LARP4/5 RNA-binding proteins in ensuring proper hemoglobin production. TENT5C catalytic mutant knock-in mice display microcytic hypochromic anemia resembling constitutive knockout. TENT5C counteracts gradual globin mRNA deadenylation during erythropoiesis. In the late stages, TENT5C dysfunction leads to globin poly(A) tail shortening and a drastic reduction of mRNA levels in reticulocytes. Proteomic experiments revealed transient but specific association of TENT5C with LARP4/5. Indeed, LARP4/5 depletion leads to downregulation and poly(A) tail shortening of globin mRNAs. Furthermore, lack of TENT5C catalytic activity is accompanied by compensatory upregulation of LARP4/5. Finally, the importance of precise regulation of globin poly(A) tails by deadenylation and re-adenylation is highlighted by the destabilization of TENT5C by CCR4-NOT deadenylase complex-associated E3 ubiquitin ligase CNOT4. O_FIG O_LINKSMALLFIG WIDTH=198 HEIGHT=200 SRC="FIGDIR/small/623596v1_ufig1.gif" ALT="Figure 1"> View larger version (59K): org.highwire.dtl.DTLVardef@82c736org.highwire.dtl.DTLVardef@1e4ea16org.highwire.dtl.DTLVardef@1c482b7org.highwire.dtl.DTLVardef@61e54a_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2024

Terminal nucleotidyltransferase Tent2 microRNA tailing regulates excitatory/inhibitory balance in the hippocampus

One of the post-transcriptional mechanisms regulating the stability of RNA molecules involves the addition of non-templated nucleotides to their 3 ends, a process known as RNA tailing. To systematically investigate the physiological consequences of terminal nucleotidyltransferase TENT2 absence on RNA 3 end modifications in the mouse hippocampus we developed a new Tent2 knockout mouse. Electrophysiological measurements revealed increased excitability in Tent2 KO hippocampal neurons, and behavioral analyses showed decreased anxiety and improved fear extinction in these mice. At the molecular level, we observed a significant contribution of TENT2 to the monoadenylation of various classes of miRNAs, but found no effect of the enzymes loss on the total poly(A) tail length of mRNAs, as measured by Direct Nanopore RNA sequencing. Alterations in monoadenylation of a large population of microRNAs affected the overall mRNA abundance, particularly transcripts related synaptic transmission, which were downregulated in the hippocampus of Tent2 knockout mice. These changes explain the observed behavioral and electrophysiological alterations. Our data thus establish a link between TENT2-dependent microRNA tailing and the balance of inhibitory and excitatory neurotransmission.

neuroscience↗

bioRxiv2024

The polyadenylation landscape after in vivo long-term potentiation in the rat brain

Local protein synthesis in neurons is vital for synaptic maintenance and plasticity, yet the regulatory mechanisms, particularly cytoplasmic polyadenylation, are not fully understood. This study employed nanopore sequencing to examine transcriptomic responses in rat hippocampi during in vivo long-term potentiation (LTP) and in synaptoneurosomes after in vitro stimulation. Our long-read transcriptomic dataset allows for detailed analysis of mRNA 3'-ends, poly(A) tail lengths, and nucleotide composition. We observed dynamic shifts in polyadenylation site preference post-LTP induction, with significant poly(A) tail lengthening restricted to transcriptionally induced mRNAs. The poly(A) tails of these genes showed increased non-adenosine abundance. In synaptoneurosomes, chemical stimulation led to shortening of poly(A) tails on preexisting mRNAs, indicating translation-induced deadenylation. Additionally, we discovered a group of neuronal transcripts with poly(A) tails abundant in non-adenosine residues. These tails are semi-templated and derived from extremely adenosine-rich 3'UTRs. This study provides a comprehensive overview of mRNA 3'-end dynamics during LTP, offering insights into post-transcriptional regulation following synaptic activation of plasticity in neurons.

neuroscience↗

bioRxiv2023

Circular extrachromosomal DNA in Euglena gracilis under normal and stress conditions

Extrachromosomal circular DNA (eccDNA) enhances genomic plasticity, augmenting its coding and regulatory potential. Advances in high-throughput sequencing have enabled the investigation of these structural variants. Although eccDNAs have been investigated in numerous taxa, they remained understudied in euglenids. Therefore, we examined eccDNAs predicted from Illumina sequencing data of Euglena gracilis Z SAG 1224-5/25, grown under optimal photoperiod and exposed to UV irradiation. We identified approximately 1000 unique eccDNA candidates, about 20% of which were shared across conditions. We also observed a significant enrichment of mitochondrially encoded eccDNA in the UV-irradiated sample. Furthermore, we found that the heterogeneity of eccDNA was reduced in UV-exposed samples compared to cells that were grown in optimal conditions. Hence, eccDNA appears to play a role in the response to oxidative stress in Euglena, as it does in other studied organisms. In addition to contributing to the understanding of Euglena genomes, our results contribute to the validation of bioinformatics pipelines on a large, non-model genome.

molecular biology↗