A5057602091- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- RNA Research and Splicing
- Circular RNAs in diseases
- RNA and protein synthesis mechanisms
- Soft tissue tumor case studies
- RNA Interference and Gene Delivery
- Oral and Maxillofacial Pathology
- Transplantation: Methods and Outcomes
- Pregnancy and preeclampsia studies
- Renal and related cancers
- Cervical Cancer and HPV Research
- Soft tissue tumors and treatment
Whitehead Institute for Biomedical Research
2020
Massachusetts Institute of Technology
2020
Howard Hughes Medical Institute
2013-2017
Rockefeller University
2013-2017
The Ohio State University
2012-2013
Significance Persistent infections with high-risk human papillomaviruses (HPVs) lead to development of cervical, penile, anal, and oropharyngeal cancers. The ability diagnose HPV has been dependent on the detection viral DNA, virus-associated cytological histological abnormalities, a few virus-induced host proteins. In this study, we identified subset microRNAs regulated specifically by HPV16 or HPV18 infection in vitro model systems. elevated expression miR-16, miR-25, miR-92a, miR-378...
Glomus tumors (GT) have been classified among of perivascular smooth muscle differentiation, together with myopericytoma, myofibroma/tosis, and angioleiomyoma, based on their morphologic overlap. However, no molecular studies carried out to date investigate genetic phenotype confirm shared pathogenesis. RNA sequencing was performed in three index cases (GT1, malignant GT; GT2, benign GT M1, multifocal myopericytoma), followed by FusionSeq data analysis, a modular computational tool developed...
MicroRNAs (miRNAs), single-stranded non-coding RNAs, influence myriad biological processes that can contribute to cancer. Although tumor-suppressive and oncogenic functions have been characterized for some miRNAs, the majority of microRNAs not investigated their ability promote modulate tumorigenesis. Here, we established miR-191/425 cluster is transcriptionally dependent on host gene, DALRD3, hormone 17β-estradiol (estrogen or E2) controls expression both DALRD3. MiR-191/425 locus...
TGF-β1 is a pleotropic growth factor that mediates glomerulosclerosis and podocyte apoptosis, hallmarks of glomerular diseases. The expression microRNA-21 (miR-21) regulated by TGF-β1, miR-21 inhibits apoptosis in cancer cells. TGF-β1–transgenic mice exhibit accelerated loss glomerulosclerosis. We determined increases rapidly cultured murine podocytes after exposure to higher kidneys than wild-type mice. miR-21–deficient showed increased proteinuria extracellular matrix deposition fewer per...
Significance MicroRNAs limit gene expression by recruiting a large protein complex known as the RNA-induced silencing (RISC) to target mRNAs. While attempting understand physiological regulation of RISC assembly, we found that most healthy adult tissues retain reserve microRNAs not stably associated with mRNA. Recruitment mRNA-containing complexes was accompanied an increase in their ability repress targets and regulated part phosphoinositide-3 kinase–RAC-alpha serine/threonine-protein...
Significance MicroRNAs (miRNAs) are short RNAs that guide the repression of most human messenger (mRNAs) and play many important roles in physiology development. To function, each miRNA associates with an Argonaute (AGO) protein to form a complex which pairs sites mRNAs, thereby targeting these mRNAs for repression, AGO TNRC6, recruits mRNA-repression machinery. For previously unknown reasons, is often more effective when miRNAs pair close one another. We find presence TNRC6 AGO-binding...
We have solved the crystal structure of human ARGONAUTE1 (hAGO1) bound to endogenous 5'-phosphorylated guide RNAs. To identify changes that evolutionarily rendered hAGO1 inactive, we compared our with guide-RNA-containing and cleavage-active hAGO2. Aside from mutation a catalytic tetrad residue, proline residues at positions 670 675 in introduce kink cS7 loop, forming convex surface within nucleic-acid-binding channel near inactive site. predicted even upon restoration tetrad, hAGO1-cS7...
MicroRNAs (miRNAs), single-stranded non-coding RNAs, influence myriad biological processes that can contribute to cancer.Although tumor-suppressive and oncogenic functions have been characterized for some miRNAs, the majority of microRNAs not investigated their ability promote modulate tumorigenesis.Here, we established miR-191/425 cluster is transcriptionally dependent on host gene, DALRD3, hormone 17b-estradiol (estrogen or E2) controls expression both DALRD3.MiR-191/425 locus...
Non-coding RNA biogenesis in higher eukaryotes has not been fully characterized. Here, we studied the Drosophila melanogaster Rexo5 (CG8368) protein, a metazoan-specific member of DEDDh 3'-5' single-stranded exonucleases, by genetic, biochemical, and RNA-sequencing approaches. is required for small nucleolar (snoRNA) rRNA essential D. melanogaster. Loss-of-function mutants accumulate improperly 3' end-trimmed 28S rRNA, 5S snoRNA precursors vivo. ubiquitously expressed at low levels somatic...
Abstract MicroRNAs (miRNAs) are small non coding RNAs that regulate gene expression at post-transcriptional level through translational inhibition and/or degradation of mRNA target genes. Recent evidence points to a widespread role for miRNAs in the initiation and progression tumorigenesis plethora tissues including mammary gland. Aberrant miRNA profiles have been described breast cancer specimens compared normal tissues, discriminating tumors with different clinico-biological phenotypes. In...