Structured cis-regulatory RNAs have evolved across all domains of life, highlighting the utility and plasticity of RNA as a regulatory molecule. Homologous RNA sequences and structures often have similar functions, but homology may also be deceiving. The challenges that derive from trying to assign function to structure and vice versa are not trivial. Bacterial riboswitches, viral and eukaryotic IRESes, CITEs, and 3' UTR elements employ an array of mechanisms to exert their effects. Bioinformatic searches coupled with biochemical and functional validation have elucidated some shared and many unique ways cis-regulators are employed in mRNA transcripts. As cis-regulatory RNAs are resolved in greater detail, it is increasingly apparent that shared homology can mask the full spectrum of mRNA cis-regulator functional diversity. Furthermore, similar functions may be obscured by lack of obvious sequence similarity. Thus looking beyond homology is crucial for furthering our understanding of RNA-based regulation.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609027 | PMC |
http://dx.doi.org/10.1042/BST20191060 | DOI Listing |
Alzheimers Dement
December 2024
Lawrence Chen Program in Neurogenetics, Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Background: Abnormal tau protein accumulation selectively affects distinct brain regions and specific neuron and glia populations in tau-related dementias like Alzheimer's disease (AD), frontotemporal dementia (FTD, Pick's disease type), and Progressive supranuclear palsy (PSP). The regulatory mechanisms governing cell-type vulnerability remain unclear.
Method: In a cross-disorder single-nucleus analysis, we examined 663,896 nuclei, assessing chromatin accessibility in three brain regions (motor cortex, visual cortex and insular cortex) across PSP, AD, and FTD in 40 individuals.
Alzheimers Dement
December 2024
Cleveland Clinic, Cleveland, OH, USA.
Background: RNA editing represents one of the most common post-transcriptional modifications that contribute to transcriptomic diversity, impacting RNA stability and regulations. To this end, we sought to investigate brain region-specific RNA-editing signatures (RNA-editings) associated with Alzheimer's disease (AD) and the human aged brain with regulatory elements.
Method: We investigated the genome-wide landscape of RNA-editings from 4,208 (1,364 AD case vs.
Alzheimers Dement
December 2024
Northwestern University, Chicago, IL, USA.
Background: Much attention has been paid to the role of the perenchymal brain immune response in Alzheimer's disease (AD). Yet, the peripheral immune system in AD has not been thoroughly studied with modern sequencing methods.
Method: Here, we used a combination of single-cell sequencing strategies, including assay for transposase-accessible chromatin and RNA sequencing, to investigate the epigenetic and transcriptional alterations to the AD peripheral immune system.
Clin Epigenetics
December 2024
Hereditary Cancer Group, ONCOBELL Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Spain.
Background: Lynch syndrome (LS), characterised by an increased risk for cancer, is mainly caused by germline pathogenic variants affecting a mismatch repair gene (MLH1, MSH2, MSH6, PMS2). Occasionally, LS may be caused by constitutional MLH1 epimutation (CME) characterised by soma-wide methylation of one allele of the MLH1 promoter. Most of these are "primary" epimutations, arising de novo without any apparent underlying cis-genetic cause, and are reversible between generations.
View Article and Find Full Text PDFNat Commun
December 2024
Department of Genetics, Yale University, Yale School of Medicine, New Haven, 06510, CT, USA.
The cis-regulatory elements encoded in an mRNA determine its stability and translational output. While there has been a considerable effort to understand the factors driving mRNA stability, the regulatory frameworks governing translational control remain more elusive. We have developed a novel massively parallel reporter assay (MPRA) to measure mRNA translation, named Nascent Peptide Translating Ribosome Affinity Purification (NaP-TRAP).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!