Biomedical subjects

William M Strauss

Publications and source records attributed to William M Strauss.

4 recordsLinked to original sources

PubMed2006

Nonrestrictive developmental regulation of microRNA gene expression.

During different periods of mammalian development, global changes in gene expression occur. Developmental changes in global gene expression have been modeled as a restrictive process. To test the restriction model of global changes in gene expression, we have used embryonic stem (ES) cells as a model system for the early mammalian embryo. ES cells are pluripotent cells that can contribute to all cellular lineages of the developing mammalian fetus and are derived from early embryonic cells. Using this model system, we have studied a new class of RNAs called microRNAs that have been identified and shown to play a role in the direct regulation of messenger RNAs. Here we report the expression signature for 248 microRNAs in 13 independent murine ES cells, embryoid bodies, and somatic tissues. The expression profile for 248 mouse microRNAs was determined for embryonic stem cells, embryoid bodies, mouse embryos, mature heart, lung, liver, kidney, and brain. Characteristic microRNA expression signatures were observed for each evaluated sample. When the characteristic microRNA signatures for developmentally ordered samples were compared, immature samples exhibited a less complex microRNA transcript profile than did mature samples. Our data support a progressive model of microRNA gene expression. Based on the progressive increase in complexity of micro- RNA expression, we hypothesize that the mammalian developmental program requires a temporal coupling of expression between microRNAs and messenger RNAs to enable the developmental potential observed in mammalian ontogeny.

Animals↗

PubMed2006

MicroRNAs in mammalian development.

Development in mammals is a complex process requiring gene expression to be spatially and temporally well-regulated. Factors modulate gene functioning by controlling transcription, translation, or mRNA degradation. microRNAs (miRNAs) are a group of small RNA molecules (approximately 22 nucleotides) that attenuate gene activity posttranscriptionally by suppressing translation or destabilizing mRNAs. miRNAs have been recently validated to regulate many animal developmental events including proliferation, differentiation, and apoptosis. Many miRNAs display intriguing expression and functioning patterns throughout these pathways. Here we will review achievements to date about studies of how miRNAs affect a variety of animal developmental transitions, from the formation of early embryos to the generation of highly specialized tissues.

Animals↗

PubMed2005

Analysis of the Xist RNA isoforms suggests two distinctly different forms of regulation.

The noncoding RNA Xist has been shown to direct the mammalian dosage compensation pathway. Expression of the Xist RNA is regulated through an uncharacterized post-transcriptional mechanism, thought to involve Xist RNA stability. We have previously demonstrated that Xist RNA isoforms contain different 3' ends. In this report we analyze the expression patterns of Xist RNA isoforms and show the Xist RNA long form (L-isoform) is the predominant form in early development. Significant amounts of both the short form (S-isoform) and the L-isoform were found in the female soma. We also define the precise sequence structure of the Xist RNA isoforms 3' ends and show the S-isoform and the L-isoform are structurally dissimilar. Our data show both the S-isoform and L-isoform are cleaved from the same primary transcript. However, the S-isoform is subsequently post-transcriptionally polyadenylated, while the L-isoform is not post-transcriptionally polyadenylated. Sequence organization of the L-isoform shows that there are at least five different nonadenylated L-isoforms in the female soma and only one in embryonic stem (ES) cells. This stem cell-and somatic cell-specific processing may suggest a role for Xist RNA processing in the regulation of Xist RNA expression.

Animals↗

PubMed2004

Telomere shortening occurs in subsets of normal breast epithelium as well as in situ and invasive carcinoma.

In the setting of inactivated DNA damage-sensitive checkpoints, critically shortened telomeres promote chromosomal instability and the types of widespread cytogenetic alterations that characterize most human carcinomas. Using a direct telomere fluorescence in situ hybridization technique, we analyzed 114 invasive breast carcinomas, 29 carcinoma in situ lesions, 10 benign proliferative lesions, and different normal epithelial components of the male and female breast. We found marked telomere shortening in the majority (52.5%) of invasive carcinomas; smaller subsets of invasive carcinoma demonstrated moderate telomere shortening (17.5%) or normal telomere lengths (21%), while a small subgroup (5%) contained elongated telomeres. Strikingly, the majority (78%) of ductal carcinoma in situ demonstrated markedly or moderately shortened telomeres. Surprisingly, unlike all other normal epithelia studied to date, moderate telomere shortening was observed in benign secretory cells in approximately 50% of histologically-normal terminal duct lobular units (from which most breast cancer is thought to arise), while such shortening was not seen in myoepithelial cells or normal large lactiferous ducts of the female breast or male breast ducts (from which breast cancer infrequently arises). We postulate that such shortening is the result of hormonally driven, physiological proliferation, and may delineate a population of epithelial cells at risk for subsequent malignant transformation.

Biomarkers, Tumor↗