Howard Hughes Medical Institute

About: Howard Hughes Medical Institute is a nonprofit organization based out in Chevy Chase, Maryland, United States. It is known for research contribution in the topics: Gene & RNA. The organization has 20371 authors who have published 34677 publications receiving 5247143 citations. The organization is also known as: HHMI & hhmi.org.

MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms

Abstract: MicroRNAs (miRNAs) are endogenously encoded small noncoding RNAs, derived by processing of short RNA hairpins, that can inhibit the translation of mRNAs bearing partially complementary target sequences. In contrast, small interfering RNAs (siRNAs), which are derived by processing of long double-stranded RNAs and are often of exogenous origin, degrade mRNAs bearing fully complementary sequences. Here, we demonstrate that an endogenously encoded human miRNA is able to cleave an mRNA bearing fully complementary target sites, whereas an exogenously supplied siRNA can inhibit the expression of an mRNA bearing partially complementary sequences without inducing detectable RNA cleavage. These data suggest that miRNAs and siRNAs can use similar mechanisms to repress mRNA expression and that the choice of mechanism may be largely or entirely determined by the degree of complementary of the RNA target.

The adult Drosophila posterior midgut is maintained by pluripotent stem cells

Abstract: Vertebrate and invertebrate digestive systems show extensive similarities in their development, cellular makeup and genetic control. The Drosophila midgut is typical: enterocytes make up the majority of the intestinal epithelial monolayer, but are interspersed with hormone-producing enteroendocrine cells. Human (and mouse) intestinal cells are continuously replenished by stem cells, the misregulation of which may underlie some common digestive diseases and cancer. In contrast, stem cells have not been described in the intestines of flies, and Drosophila intestinal cells have been thought to be relatively stable. Here we use lineage labelling to show that adult Drosophila posterior midgut cells are continuously replenished by a distinctive population of intestinal stem cells (ISCs). As in vertebrates, ISCs are multipotent, and Notch signalling is required to produce an appropriate fraction of enteroendocrine cells. Notch is also required for the differentiation of ISC daughter cells, a role that has not been addressed in vertebrates. Unlike previously characterized stem cells, which reside in niches containing a specific partner stromal cell, ISCs adjoin only the basement membrane, differentiated enterocytes and their most recent daughters. The identification of Drosophila intestinal stem cells with striking similarities to their vertebrate counterparts will facilitate the genetic analysis of normal and abnormal intestinal function.

The UCSC Genome Browser database: 2015 update

Abstract: Launched in 2001 to showcase the draft human genome assembly, the UCSC Genome Browser database (http://genome.ucsc.edu) and associated tools continue to grow, providing a comprehensive resource of genome assemblies and annotations to scientists and students worldwide. Highlights of the past year include the release of a browser for the first new human genome reference assembly in 4 years in December 2013 (GRCh38, UCSC hg38), a watershed comparative genomics annotation (100-species multiple alignment and conservation) and a novel distribution mechanism for the browser (GBiB: Genome Browser in a Box). We created browsers for new species (Chinese hamster, elephant shark, minke whale), 'mined the web' for DNA sequences and expanded the browser display with stacked color graphs and region highlighting. As our user community increasingly adopts the UCSC track hub and assembly hub representations for sharing large-scale genomic annotation data sets and genome sequencing projects, our menu of public data hubs has tripled.

Crystal structure of a yeast TBP/TATA-box complex.

Abstract: The 2.5 A crystal structure of a TATA-box complex with yeast TBP shows that the eight base pairs of the TATA box bind to the concave surface of TBP by bending towards the major groove with unprecedented severity. This produces a wide open, underwound, shallow minor groove which forms a primarily hydrophobic interface with the entire under-surface of the TBP saddle. The severe bend and a positive writhe radically alter the trajectory of the flanking B-form DNA.