Noncoding RNA has arrived at centre stage in recent years with the discovery of "hidden transcriptomes" in many higher organisms. Over two decades ago, noncoding transcripts were discovered in Drosophila Hox complexes, but their function has remained elusive. Recent studies1-3 have examined the role of these noncoding RNAs in Hox gene regulation, and have generated a fierce debate as to whether the noncoding transcripts are important for silencing or activation. Here we review the evidence, and show that, by taking developmental timing into account, some of these apparently conflicting results can be resolved. We examine current models that explain these data and explore alternative interpretations.
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http://dx.doi.org/10.1002/bies.20704 | DOI Listing |
Alzheimers Dement
December 2024
Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Background: Recent studies suggest genome-wide-association-studies (GWAS) loci confer their effects on microglia in late-onset Alzheimer's disease (LOAD) brains. Relatively fewer studies have investigated the effects of other genome-wide significant loci (p<5e) using human neurons.
Method: GWAS itself cannot directly identify causal variant-(effector)gene-pairs as GWAS only reports the sentinel variant at a given locus.
Alzheimers Dement
December 2024
Homi Bhabha National Institute, Mumbai, Maharashtra, India.
Background: Recent advances in understanding the regulatory networks implicated in Alzheimer's Disease (AD) evinces the involvement of long non-coding RNAs (lncRNAs) as crucial regulatory players. The present study explores the role played by maternally imprinted lncRNA XIST in regulating the sex-biased prevalence of AD.
Method: With whole transcriptomic sequencing data from the hippocampal RNA of post-mortem AD brains from humans and APP/PS1 mice, the altered expression of XIST in AD was studied.
Alzheimers Dement
December 2024
Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
Background: Annotation of target genes of non-coding GWAS loci remains a challenge since 1) regulatory elements identified by GWAS can be metabases away from its actual target, 2) one regulatory element can target multiple genes, and 3) multiple regulatory elements can target one gene. AD GWAS in populations with different ancestries have identified different loci, suggesting ancestry-specific genetic risks. To understand the connection between associated loci (potential regulatory elements) and their target genes, we conducted Hi-C analysis in frontal cortex of African American (AA) and Non-Hispanic Whites (NHW) AD patients to map chromatin loops, which often represent enhancer-promoter (EP) interactions.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of California, Irvine, Irvine, CA, USA.
Background: Genome-Wide Association Studies (GWAS) implicate SPI1 (PU.1) as a risk factor for late-onset Alzheimer's Disease (LOAD). Within the brain, SPI1 encodes a microglia-specific transcription factor, necessary for microglial proliferation and activation.
View Article and Find Full Text PDFInt J Cancer
January 2025
Laboratory of Onco-Hematology, Necker Children's Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France.
T-cell acute lymphoblastic leukaemia (T-ALL) is a rare aggressive haematological malignancy characterised by the clonal expansion of immature T-cell precursors. It accounts for 15% of paediatric and 25% of adult ALL. T-ALL is associated with the overexpression of major transcription factors (TLX1/3, TAL1, HOXA) that drive specific transcriptional programmes and constitute the molecular classifying subgroups of T-ALL.
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