mRNA Quality Control in the Aging of Nematode Worms
The nematode worm species Caenorhabditis elegans widely used in the laboratory is far removed from human biochemistry, but nonetheless there is much that can be learned about cellular mechanisms relevant to the aging of mammals. Here researchers review what is known of the role of messenger RNA (mRNA) quality control mechanisms in the aging of nematodes. mRNA is produced from gene sequences in the process of transcription, but every operation in the cell is subject to some level of error and happenstance damage to molecular structure. Thus quality control systems must exist to ensure that broken mRNA molecules do not lead to harmful outcomes, such as the production of broken, toxic proteins.
Aging is accompanied by the gradual decline in cellular and organismal fitness. At the macromolecular level, impaired protein homeostasis (proteostasis) and genome integrity are key features of aging. The age-dependent deteriorative changes are interconnected with each other to decrease the lifespan and increase the incidence of age-associated diseases, which eventually lead to death. Similar to other species, C. elegans exhibits age-associated changes such as the reduction in genome stability, proteostasis, lipid homeostasis, and immunity. Recent studies have indicated that RNA quality also declines during aging in C. elegans.
Eukaryotes are equipped with homeostatic systems that are crucial for the maintenance of mRNA quality, which is regulated by diverse surveillance pathways. Misprocessed mRNAs need to be eliminated by these RNA surveillance pathways. Nonsense-mediated mRNA decay (NMD), no-go decay, nonstop decay, and ribosome-associated quality control (RQC) are crucial for mRNA and protein quality control. mRNA splicing, which is a major pre-mRNA processing event in eukaryotes, selects and joins exons that are separated by introns, thus enabling diverse gene expression. Changes in splicing occur during aging and may reflect the deteriorated transcriptome quality. Abnormal mRNA splicing underlies the generation of aberrant transcripts that disrupts the proteostasis by producing truncated proteins and causing ribosome stalling, followed by ribosome collision.
Here we review recent studies that report on the key functions of various factors that regulate mRNA surveillance and splicing in the longevity and aging of C. elegans. Our review provides crucial information regarding the conserved functions of mRNA quality control in aging, which may be potentially utilized as therapeutic targets of aging and age-associated diseases in humans.
Interesting! I wonder if mRNA quality control differs between somatic, stem, and germ cells.