5′ and 3′ modifications controlling RNA degradation: from safeguards to executioners

Abstract

RNA degradation is a key process in the regulation of gene expression. In all organisms, RNA degradation participates in controlling coding and non-coding RNA levels in response to developmental and environmental cues. RNA degradation is also crucial for the elimination of defective RNAs. Those defective RNAs are mostly produced by ‘mistakes’ made by the RNA processing machinery during the maturation of functional transcripts from their precursors. The constant control of RNA quality prevents potential deleterious effects caused by the accumulation of aberrant non-coding transcripts or by the translation of defective messenger RNAs (mRNAs). Prokaryotic and eukaryotic organisms are also under the constant threat of attacks from pathogens, mostly viruses, and one common line of defence involves the ribonucleolytic digestion of the invader's RNA. Finally, mutations in components involved in RNA degradation are associated with numerous diseases in humans, and this together with the multiplicity of its roles illustrates the biological importance of RNA degradation. RNA degradation is mostly viewed as a default pathway: any functional RNA (including a successful pathogenic RNA) must be protected from the scavenging RNA degradation machinery. Yet, this protection must be temporary, and it will be overcome at one point because the ultimate fate of any cellular RNA is to be eliminated. This special issue focuses on modifications deposited at the 5′ or the 3′ extremities of RNA, and how these modifications control RNA stability or degradation. This article is part of the theme issue ‘5′ and 3′ modifications controlling RNA degradation’.

On the Way to Understanding the Interplay between the RNA Structure and Functions in Cells: A Genome-Wide Perspective

“…The stability and fate of mRNA molecules in the cell are under strict control, and at the end of their life cycle, RNAs undergo a carefully regulated degradation. The cap at the 5′-end and the poly(A) tail at the 3′-end are considered as major determinants of mRNA stability, but it can be also regulated by the other intrinsic features of transcripts, such as the sequence, length, and structure of UTRs and RNA modifications in UTRs [ 3 , 48 , 49 , 67 , 68 ]. Transcriptome-wide studies in vivo provide a growing number of evidence that RNA structural features can govern the RNA lifespan ( Table 2 ).…”

Omics Analysis of Educated Platelets in Cancer and Benign Disease of the Pancreas

“…For example, we found that many miRNAs related to the RNA splicing pathway, where up-regulated in PDAC platelets, whereas the mature mRNAs associated to them where down-regulated. This may suggest that other regulatory mechanisms are involved in mature-RNA degradation such as 5′ and 3′ modifications on RNA extremities [ 61 ], RNA helicases, poly-A tail elongation, chaperones and silencing RNAs (psiRNAs) [ 62 ]. However, integrated pathway analysis showed that miRNAs correlated with protein levels, meaning that, also when mRNA is degraded, proteins are still produced.…”

Synthetic modified messenger RNA for therapeutic applications

“…The cap mimics in synthetic mRNA were designed and made in order to enhance its translation efficiency and stability, as well as to reduce intracellular innate immunogenicity by impeding stimulation of RIG-I [ 35 , 36 ] ( Fig. 2 B ).…”