Next Article in Journal
Viroids: Non-Coding Circular RNAs Able to Autonomously Replicate and Infect Higher Plants
Next Article in Special Issue
Selection and Evaluation of mRNA and miRNA Reference Genes for Expression Studies (qPCR) in Archived Formalin-fixed and Paraffin-embedded (FFPE) Colon Samples of DSS-induced Colitis Mouse Model
Previous Article in Journal
Quantitative Load Dependency Analysis of Local Trabecular Bone Microstructure to Understand the Spatial Characteristics in the Synthetic Proximal Femur
Previous Article in Special Issue
BioTEA: Containerized Methods of Analysis for Microarray-Based Transcriptomics Data
 
 
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Selective Destabilization of Transcripts by mRNA Decapping Regulates Oocyte Maturation and Innate Immunity Gene Expression during Ageing in C. elegans

1
Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece
2
Center of Systems Biology, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece
*
Authors to whom correspondence should be addressed.
Current address: Department of Biology, University of Padova, 35121 Padova, Italy.
Current address: Institute of Biochemistry, Charité Universitätsmedizin, 10117 Berlin, Germany.
§
Current address: Biobank.cy Center of Excellence in Biobanking and Biomedical Research, University of Cyprus, 2029 Nicosia, Cyprus.
Biology 2023, 12(2), 171; https://doi.org/10.3390/biology12020171
Received: 1 December 2022 / Revised: 13 January 2023 / Accepted: 20 January 2023 / Published: 21 January 2023
(This article belongs to the Special Issue Differential Gene Expression and Coexpression)

Simple Summary

In eukaryotes, the elimination of the protective cap from 5′ end of messenger RNA (mRNA) by the decapping complex is an important mechanism of mRNA decay and translation, affecting several cellular processes. In the nematode C. elegans, perturbations in decapping activity slow development and shorten the lifespan. A microarray analysis performed in mid-aged nematodes with reduced decapping activity revealed a specific role for decapping in the suppression of spermatogenic genes in germ cells during ageing. In addition, the expression of many innate immunity and detoxification genes were upregulated in the somatic cells of the mutant nematodes, despite the lack of pathogens. This upregulation appears to be mediated by the effect of aberrant decapping on both the mRNA stability and the nuclear translocation of the transcription factor PQM-1, which controls the expression of those immunity/detoxification genes. Although the decapping-mediated induction of immunity was found to be detrimental for the normal lifespan, it mitigates the paralysis in a C. elegans model of polyglutamine toxicity. These results reinforce the selectivity of decapping in the regulation of gene expression and provide a link between mRNA decapping and innate immunity in older ages that could serve as a protective mechanism for disturbed proteostasis, commonly associated with human neurodegenerative diseases.

Abstract

Removal of the 5′ cap structure of RNAs (termed decapping) is a pivotal event in the life of cytoplasmic mRNAs mainly catalyzed by a conserved holoenzyme, composed of the catalytic subunit DCP2 and its essential cofactor DCP1. While decapping was initially considered merely a step in the general 5′-3′ mRNA decay, recent data suggest a great degree of selectivity that plays an active role in the post-transcriptional control of gene expression, and regulates multiple biological functions. Studies in Caenorhabditis elegans have shown that old age is accompanied by the accumulation of decapping factors in cytoplasmic RNA granules, and loss of decapping activity shortens the lifespan. However, the link between decapping and ageing remains elusive. Here, we present a comparative microarray study that was aimed to uncover the differences in the transcriptome of mid-aged dcap-1/DCP1 mutant and wild-type nematodes. Our data indicate that DCAP-1 mediates the silencing of spermatogenic genes during late oogenesis, and suppresses the aberrant uprise of immunity gene expression during ageing. The latter is achieved by destabilizing the mRNA that encodes the transcription factor PQM-1 and impairing its nuclear translocation. Failure to exert decapping-mediated control on PQM-1 has a negative impact on the lifespan, but mitigates the toxic effects of polyglutamine expression that are involved in human disease.
Keywords: mRNA decapping; ageing; spermatogenesis; innate immunity; polyglutamine; microarray; C. elegans; DCAP-1; PQM-1 mRNA decapping; ageing; spermatogenesis; innate immunity; polyglutamine; microarray; C. elegans; DCAP-1; PQM-1

Share and Cite

MDPI and ACS Style

Borbolis, F.; Ranti, D.; Papadopoulou, M.-D.; Dimopoulou, S.; Malatras, A.; Michalopoulos, I.; Syntichaki, P. Selective Destabilization of Transcripts by mRNA Decapping Regulates Oocyte Maturation and Innate Immunity Gene Expression during Ageing in C. elegans. Biology 2023, 12, 171. https://doi.org/10.3390/biology12020171

AMA Style

Borbolis F, Ranti D, Papadopoulou M-D, Dimopoulou S, Malatras A, Michalopoulos I, Syntichaki P. Selective Destabilization of Transcripts by mRNA Decapping Regulates Oocyte Maturation and Innate Immunity Gene Expression during Ageing in C. elegans. Biology. 2023; 12(2):171. https://doi.org/10.3390/biology12020171

Chicago/Turabian Style

Borbolis, Fivos, Dimitra Ranti, Maria-Despina Papadopoulou, Sofia Dimopoulou, Apostolos Malatras, Ioannis Michalopoulos, and Popi Syntichaki. 2023. "Selective Destabilization of Transcripts by mRNA Decapping Regulates Oocyte Maturation and Innate Immunity Gene Expression during Ageing in C. elegans" Biology 12, no. 2: 171. https://doi.org/10.3390/biology12020171

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop