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Duff, M. O.

Publications and source records attributed to Duff, M. O..

2 recordsLinked to original sources

A Large-Scale Binding and Functional Map of Human RNA Binding Proteins

Genomes encompass all the information necessary to specify the development and function of an organism. In addition to genes, genomes also contain a myriad of functional elements that control various steps in gene expression. A major class of these elements function only when transcribed into RNA as they serve as the binding sites for RNA binding proteins (RBPs), which act to control post-transcriptional processes including splicing, cleavage and polyadenylation, RNA editing, RNA localization, stability, and translation. Despite the importance of these functional RNA elements encoded in the genome, they have been much less studied than genes and DNA elements. Here, we describe the mapping and characterization of RNA elements recognized by a large collection of human RBPs in K562 and HepG2 cells. These data expand the catalog of functional elements encoded in the human genome by addition of a large set of elements that function at the RNA level through interaction with RBPs.\n\nHighlightsO_LI223 eCLIP datasets for 150 RBPs reveal a wide variety of in vivo RNA target classes.\nC_LIO_LI472 knockdown/RNA-seq profiles of 263 RBPs reveal factor-responsive targets and integration with eCLIP indicates RNA expression and splicing regulatory patterns.\nC_LIO_LI78 RNA Bind-N-Seq profiles of in vitro binding motifs reveal links between in vitro and in vivo binding and indicate that eCLIP peaks that contain in vitro motifs are more strongly associated with regulation.\nC_LIO_LI274 maps of RBP subcellular localization by immunofluorescence indicate widespread organelle-specific RNA processing regulation.\nC_LIO_LI63 ChIP-seq profiles of DNA association suggest broad interconnectivity between chromatin association and RNA processing.\nC_LI

genomics

Red Blood Cell Distribution Width: genetic evidence for aging pathways in 116,666 volunteers

Variability in red blood cell volumes (distribution width, RDW) increases with age and is strongly predictive of mortality, incident coronary heart disease and cancer. We investigated inherited genetic variation associated with RDW in 166,666 UK Biobank human volunteers.\n\nA large proportion RDW is explained by genetic variants (29%), especially in the older group (60+ year olds, 33.8%, <50 year olds, 28.4%). RDW was associated with 194 independent genetic signals; 71 are known for conditions including autoimmune disease, certain cancers, BMI, Alzheimers disease, longevity, age at menopause, bone density, myositis, Parkinsons disease, and age-related macular degeneration. Pathways analysis showed enrichment for telomere maintenance, ribosomal RNA and apoptosis.\n\nAlthough increased RDW is predictive of cardiovascular outcomes, this was not explained by known CVD or related lipid genetic risks. The predictive value of RDW for a range of negative health outcomes may in part be due to variants influencing fundamental pathways of aging.

genomics