Mining Functional Elements in Messenger RNAs: Overview, Challenges, and Perspectives

Abstract

Eukaryotic messenger RNA (mRNA) contains not only protein-coding regions but also a plethora of functional cis-elements that influence or coordinate a number of regulatory aspects of gene expression, such as mRNA stability, splicing forms, and translation rates. Understanding the rules that apply to each of these element types (e.g., whether the element is defined by primary or higher-order structure) allows for the discovery of novel mechanisms of gene expression as well as the design of transcripts with controlled expression. Bioinformatics plays a major role in creating databases and finding non-evident patterns governing each type of eukaryotic functional element. Much of what we currently know about mRNA regulatory elements in eukaryotes is derived from microorganism and animal systems, with the particularities of plant systems lagging behind. In this review, we provide a general introduction to the most well-known eukaryotic mRNA regulatory motifs (splicing regulatory elements, internal ribosome entry sites, iron-responsive elements, AU-rich elements, zipcodes, and polyadenylation signals) and describe available bioinformatics resources (databases and analysis tools) to analyze eukaryotic transcripts in search of functional elements, focusing on recent trends in bioinformatics methods and tool development. We also discuss future directions in the development of better computational tools based upon current knowledge of these functional elements. Improved computational tools would advance our understanding of the processes underlying gene regulations. We encourage plant bioinformaticians to turn their attention to this subject to help identify novel mechanisms of gene expression regulation using RNA motifs that have potentially evolved or diverged in plant species.

Integrated Network Analysis Reveals FOXM1 and MYBL2 as Key Regulators of Cell Proliferation in Non-small Cell Lung Cancer

“…Our study suggested that a gene could be functionally important even at a small level of overexpression such as FOXM1 and MYBL2 if they act as upstream regulators of genes of interacting proteins involved in an important biological process (20). However, our study has following limitations: (a) All the findings are based upon computational analysis using integrated data of gene expression, PPI, TFs, and miRNAs; (b) Our study did not integrate the data of gene mutations and gene copy number variations, which could abolish the cis- and trans-regulatory elements of a gene resulting aberrant gene expression and cancer (96–98); and (c) Finally, our study lacks the experimental validation and therefore need further experimental testing.…”

Plant cytoplasmic GAPDH: redox post-translational modifications and moonlighting properties

“…AREs are common cis-regulatory elements of 3′-untranslated regions (UTR) of eukaryotic messenger RNAs and are important determinants of mRNA stability in mammals. Proteins binding to these elements can either increase or decrease mRNA stability and thus affect protein expression levels ( Ahmed et al, 2011 ). The mRNA of the endothelin ET-1 contains in its 3′-UTR an ARE forming a secondary structure.…”

Viral IRES Prediction System - a Web Server for Prediction of the IRES Secondary Structure In Silico

“…However, to improve sensitivity and specificity of cellular IRES elements in VIPS, new algorithms can be implemented to simulate real relationships and interactions between 40s rRNA and IRES elements in next version of our prediction system. The new bioinformatic tool plays a major role in creating databases and finding eukaryotic functional elements such as IRES, iron-responsive elements, splicing regulatory elements.. etc [28]. Therefore, VIPS will be a useful internet resource for IRES elements location before experimental studies.…”