Dynamic Variations of 3′UTR Length Reprogram the mRNA Regulatory Landscape

Abstract

This paper concerns 3′-untranslated regions (3′UTRs) of mRNAs, which are non-coding regulatory platforms that control stability, fate and the correct spatiotemporal translation of mRNAs. Many mRNAs have polymorphic 3′UTR regions. Controlling 3′UTR length and sequence facilitates the regulation of the accessibility of functional effectors (RNA binding proteins, miRNAs or other ncRNAs) to 3′UTR functional boxes and motifs and the establishment of different regulatory landscapes for mRNA function. In this context, shortening of 3′UTRs would loosen miRNA or protein-based mechanisms of mRNA degradation, while 3′UTR lengthening would strengthen accessibility to these effectors. Alterations in the mechanisms regulating 3′UTR length would result in widespread deregulation of gene expression that could eventually lead to diseases likely linked to the loss (or acquisition) of specific miRNA binding sites. Here, we will review the mechanisms that control 3′UTR length dynamics and their alterations in human disorders. We will discuss, from a mechanistic point of view centered on the molecular machineries involved, the generation of 3′UTR variability by the use of alternative polyadenylation and cleavage sites, of mutually exclusive terminal alternative exons (exon skipping) as well as by the process of exonization of Alu cassettes to generate new 3′UTRs with differential functional features.

Genome-Wide Analysis of SAUR Gene Family Identifies a Candidate Associated with Fruit Size in Loquat (Eriobotrya japonica Lindl.)

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Molecular Mechanisms Underlying the Elevated Expression of a Potentially Type 2 Diabetes Mellitus Associated SCD1 Variant

“…In general, polymorphisms in the 3‘UTR as well as other variants (e.g., length, regulation by miRNAs, etc.) affect mRNA degradation [ 45 ], and there is also evidence in the literature that common variants of the coding region, even synonymous SNPs, may also alter mRNA stability [ 46 ]. Our assumption is substantiated by an extra hairpin loop predicted in the flanking region of the polymorphic site in the minor variant in silico ( Figure 2 b,c) and confirmed by a hindered mRNA degradation seen after actinomycin D treatment in vitro ( Figure 2 d).…”

A common whole-genome paleotetraploidization in Cucurbitales

“…Gene structural diversity may promote protein functional diversity. The CDS contains exons that encode protein sequences, and the UTR is a noncoding region at either end of the mRNA that contains many different regulatory elements involved in variable splicing ( Mayr, 2019 ; Navarro et al, 2021 ). For the gene structures of the families in Cucurbitales involved in the CS pathway, we found that the Cucurbitaceae shows more diversity than Begoniaceae.…”