scholarly journals Exon–Intron Differential Analysis Reveals the Role of Competing Endogenous RNAs in Post-Transcriptional Regulation of Translation

2021 ◽  
Vol 7 (2) ◽  
pp. 26
Author(s):  
Nicolas Munz ◽  
Luciano Cascione ◽  
Luca Parmigiani ◽  
Chiara Tarantelli ◽  
Andrea Rinaldi ◽  
...  
Keyword(s):  
Dna Damage ◽  
Transcriptional Regulation ◽  
Translational Regulation ◽  
Mammalian Target Of Rapamycin ◽  
B Cell Lymphoma ◽  
Protein Translation ◽  
Differential Analysis ◽  
Regulation Of Translation ◽  
Save Energy ◽  
Post Transcriptional Regulation

Stressful conditions induce the cell to save energy and activate a rescue program modulated by mammalian target of rapamycin (mTOR). Along with transcriptional and translational regulation, the cell relies also on post-transcriptional modulation to quickly adapt the translation of essential proteins. MicroRNAs play an important role in the regulation of protein translation, and their availability is tightly regulated by RNA competing mechanisms often mediated by long noncoding RNAs (lncRNAs). In our paper, we simulated the response to growth adverse condition by bimiralisib, a dual PI3K/mTOR inhibitor, in diffuse large B cell lymphoma cell lines, and we studied post-transcriptional regulation by the differential analysis of exonic and intronic RNA expression. In particular, we observed the upregulation of a lncRNA, lncTNK2-2:1, which correlated with the stabilization of transcripts involved in the regulation of translation and DNA damage after bimiralisib treatment. We identified miR-21-3p as miRNA likely sponged by lncTNK2-2:1, with consequent stabilization of the mRNA of p53, which is a master regulator of cell growth in response to DNA damage.

scholarly journals Post-transcriptional regulation of Leishmania fitness gain

2021 ◽  
Author(s):  
Laura Piel ◽  
K. Shanmugha Rajan ◽  
Giovanni Bussotti ◽  
Hugo Varet ◽  
Rachel Legendre ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Leishmania Donovani ◽  
Biomarker Discovery ◽  
Genome Instability ◽  
Gene Dosage ◽  
Protein Translation ◽  
Gene Dosage Effects ◽  
Dosage Effects ◽  
Post Transcriptional Regulation

The protozoan parasite Leishmania donovani causes fatal human visceral leishmaniasis in absence of treatment. Genome instability has been recognized as a driver in Leishmania fitness gain in response to environmental change or chemotherapy. How genome instability generates beneficial phenotypes despite potential deleterious gene dosage effects is unknown. Here we address this important open question applying experimental evolution and integrative systems approaches on parasites adapting to in vitro culture. Phenotypic analyses of parasites from early and late stages of culture adaptation revealed an important fitness tradeoff, with selection for accelerated growth (fitness gain) impairing infectivity (fitness costs). Comparative genomics, transcriptomics and proteomics analyses revealed a complex regulatory network driving parasite fitness, with genome instability causing highly reproducible, gene dosage-dependent changes in protein linked to post-transcriptional regulation. These in turn were associated with a gene dosage-independent reduction in flagellar transcripts and a coordinated increase in abundance of coding and non-coding RNAs known to regulate ribosomal biogenesis and protein translation. We correlated differential expression of small nucleolar RNAs (snoRNAs) with changes in rRNA modification, providing first evidence that Leishmania fitness gain may be controlled by post-transcriptional and epitranscriptomic regulation. Our findings propose a novel model for Leishmania fitness gain, where differential regulation of mRNA stability and the generation of fitness-adapted ribosomes may potentially filter deleterious from beneficial gene dosage effects and provide proteomic robustness to genetically heterogenous, adapting parasite populations. This model challenges the current, genome-centric approach to Leishmania epidemiology and identifies the Leishmania non-coding small RNome as a potential novel source for biomarker discovery.

scholarly journals Dietary restriction induces post-transcriptional regulation of longevity genes

2019 ◽  
Author(s):  
Jarod A. Rollins ◽  
Santina S. Snow ◽  
Pankaj Kapahi ◽  
Aric N. Rogers
Keyword(s):  
Transcriptional Regulation ◽  
Dietary Restriction ◽  
Translational Regulation ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Intron Retention ◽  
Translation Efficiency ◽  
Nonsense Mediated Decay ◽  
Longevity Genes ◽  
Post Transcriptional Regulation

AbstractDietary restriction increases lifespan through adaptive changes in gene expression. To understand more about these changes, we analyzed the transcriptome and translatome of C. elegans subjected to dietary restriction. Transcription of muscle regulatory and structural genes increased, while increased expression of amino acid metabolism and neuropeptide signaling genes was controlled at the level of translation. Evaluation of post-transcriptional regulation identified putative roles for RNA binding proteins, RNA editing, microRNA, alternative splicing, and nonsense mediated decay in response to nutrient limitation. Using RNA interference, we discovered several differentially expressed genes that regulate lifespan. We also found a compensatory role for translational regulation, which offsets dampened expression of a large subset of transcriptionally downregulated genes. Furthermore, 3’ UTR editing and intron retention increase under dietary restriction and correlate with diminished translation, while trans-spliced genes are refractory to reduced translation efficiency compared to messages with the native 5’ UTR. Finally, we find that smg-6 and smg-7, which are genes governing selection and turnover of nonsense mediated decay targets, are required for increased lifespan under dietary restriction.

scholarly journals Diversity of RNA-Binding Proteins Modulating Post-Transcriptional Regulation of Protein Expression in the Maturing Mammalian Oocyte

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 662 ◽  
Author(s):  
Marie Christou-Kent ◽  
Magali Dhellemmes ◽  
Emeline Lambert ◽  
Pierre F. Ray ◽  
Christophe Arnoult
Keyword(s):  
Transcriptional Regulation ◽  
Translational Regulation ◽  
Binding Proteins ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Current Knowledge ◽  
Early Embryo ◽  
Developmental Competence ◽  
Gene Expression Control ◽  
Post Transcriptional Regulation

The oocyte faces a particular challenge in terms of gene regulation. When oocytes resume meiosis at the end of the growth phase and prior to ovulation, the condensed chromatin state prevents the transcription of genes as they are required. Transcription is effectively silenced from the late germinal vesicle (GV) stage until embryonic genome activation (EGA) following fertilisation. Therefore, during its growth, the oocyte must produce the mRNA transcripts needed to fulfil its protein requirements during the active period of meiotic completion, fertilisation, and the maternal-to zygote-transition (MZT). After meiotic resumption, gene expression control can be said to be transferred from the nucleus to the cytoplasm, from transcriptional regulation to translational regulation. Maternal RNA-binding proteins (RBPs) are the mediators of translational regulation and their role in oocyte maturation and early embryo development is vital. Understanding these mechanisms will provide invaluable insight into the oocyte’s requirements for developmental competence, with important implications for the diagnosis and treatment of certain types of infertility. Here, we give an overview of post-transcriptional regulation in the oocyte, emphasising the current knowledge of mammalian RBP mechanisms, and develop the roles of these mechanisms in the timely activation and elimination of maternal transcripts.

43-OR: Post-transcriptional Regulation of Slc16a1 mRNA Is Essential for Maintaining Normal ß-Cell Function

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 43-OR
Author(s):  
DINA MOSTAFA ◽  
AKINORI TAKAHASHI ◽  
TADASHI YAMAMOTO
Keyword(s):  
Transcriptional Regulation ◽  
Cell Function ◽  
Post Transcriptional Regulation
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