6 research outputs found
Global assessment of GU-rich regulatory content and function in the human transcriptome
Unlike AU-rich elements (ARes) that are largely present in the 3′UTRs of many unstable mammalian mRNAs, the function and abundance of GU-rich elements (GRes) are poorly understood. We performed a genome-wide analysis and found that at least 5% of human genes contain GRes in their 3′UTRs with functional over-representation in genes involved in transcription, nucleic acid metabolism, developmental processes and neurogenesis. GRes have similar sequence clustering patterns with ARes such as overlapping GUUUG pentamers and enrichment in 3′UTRs. Functional analysis using T-cell mRNA expression microarray data confirms correlation with mRNA destabilization. Reporter assays show that compared with ARes the ability of GRes to destabilize mRNA is modest and does not increase with the increasing number of overlapping pentamers. Naturally occurring GREs within U-rich contexts were more potent in destabilizing GFP reporter mRNAs than synthetic GREs with perfectly overlapping pentamers. Overall, we find that GREs bear a resemblance to AREs in sequence patterns but they regulate a different repertoire of genes and have different dynamics of mRNA decay. A dedicated resource on all GRE-containing genes of the human, mouse and rat genomes can be found at brp.kfshrc.edu.sa/GredOrg
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Distribution of hand function by age in individuals with Rett syndrome
Abstract:
Objective:
We aimed to determine the longitudinal distribution of hand function skills in individuals with classic Rett syndrome (RTT), an X‐linked dominant neurodevelopmental disorder, and correlate with MECP2 variants.
Method:
We conducted a longitudinal study of 946 girls and young women with typical RTT seen between 2006 and 2021 in the US Natural History Study (NHS) featuring a structured clinical evaluation to assess the level of hand function skills. The specific focus of this study was to assess longitudinal variation of hand skills from age 2 through age 18 years in relation to specific MECP2 variant groups.
Results:
Following the initial regression period, hand function continues to decline across the age spectrum in individuals with RTT. Specific differences are noted with steeper declines in hand function among those with milder variants (Group A: R133C, R294X, R306C, and C‐terminal truncations) compared with groups composed of individuals with more severe variants.
Conclusions:
These temporal variations in hand use represent specific considerations that could influence the design of clinical trials that test therapies aiming to ameliorate specific functional limitations in individuals with RTT. Furthermore, the distinct impact of specific MECP2 variants on clinical severity, especially related to hand use, should be considered in such interventional trials