A5065770106- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- RNA modifications and cancer
- RNA Interference and Gene Delivery
- MicroRNA in disease regulation
- Epigenetics and DNA Methylation
- Pluripotent Stem Cells Research
- RNA and protein synthesis mechanisms
- DNA Repair Mechanisms
- Influenza Virus Research Studies
- interferon and immune responses
- Immune Cell Function and Interaction
- Acute Myeloid Leukemia Research
- Cytokine Signaling Pathways and Interactions
- Chromosomal and Genetic Variations
- Tissue Engineering and Regenerative Medicine
- HIV Research and Treatment
- Cancer-related molecular mechanisms research
- Animal Genetics and Reproduction
- Reproductive Biology and Fertility
- Protein Degradation and Inhibitors
- RNA regulation and disease
- Renal and related cancers
- Viral Infections and Outbreaks Research
University of California, Riverside
2020-2025
Harvard Stem Cell Institute
2012-2018
Harvard University
2013-2018
Massachusetts General Hospital
2012-2018
Howard Hughes Medical Institute
2008-2016
Cold Spring Harbor Laboratory
2005-2012
St. Jude Children's Research Hospital
2005-2012
Stony Brook University
2010
King's College London
2006
University College London
2006
Dicer is a central enzyme in microRNA (miRNA) processing. We identified Dicer-independent miRNA biogenesis pathway that uses Argonaute2 (Ago2) slicer catalytic activity. In contrast to other miRNAs, miR-451 levels were refractory dicer loss of function but reduced MZago2 (maternal-zygotic) mutants. found pre-miR-451 processing requires Ago2 activity vivo. mutants showed delayed erythropoiesis could be rescued by wild-type or miR-451-duplex not catalytically dead Ago2. Changing the secondary...
Dicer is an RNase III-family nuclease that initiates RNA interference (RNAi) and related phenomena by generation of the small RNAs determine specificity these gene silencing pathways. We have previously shown essential for mammalian development, with Dicer-deficient mice dying at embryonic day 7.5 a lack detectable multipotent stem cells. To permit more detailed investigation biological roles Dicer, we generated cell lines in which their single can be conditionally inactivated. As expected,...
The canonical microRNA (miRNA) biogenesis pathway requires two RNaseIII enzymes: Drosha and Dicer. To understand their functions in mammals vivo, we engineered mice with germline or tissue-specific inactivation of the genes encoding these proteins. Changes proteomic transcriptional profiles that were shared Dicer- Drosha-deficient confirmed requirement for both enzymes miRNA biogenesis. However, deficiency Dicer did not always result identical phenotypes, suggesting additional functions. We...
How RNA-binding proteins (RBPs) convey regulatory instructions to the core effectors of RNA processing is unclear. Here, we document existence and functions a multivalent RBP-effector interface. We show that effector interface conserved RBP with an essential role in metazoan development, Unkempt, mediated by novel type 'dual-purpose' peptide motifs can contact two different surfaces interacting proteins. Unexpectedly, find contacts do not merely serve recruitment but are required for...
Stem and progenitor cells have the capacity to balance self-renewal differentiation. Hematopoietic myeloid progenitors replenish more than 25 billion terminally differentiated neutrophils every day under homeostatic conditions can increase this output in response stress or infection. At what point along spectrum of maturation do lose for become irreversibly committed differentiation? Using a system conditional development that be toggled between differentiation, we interrogate determinants...
Cellular morphology is an essential determinant of cellular function in all kingdoms life, yet little known about how cell shape controlled. Here we describe a molecular program that controls the early neurons through metazoan-specific zinc finger protein, Unkempt. Depletion Unkempt mouse embryos disrupts migrating neurons, while ectopic expression confers neuronal-like to cells different nonneuronal lineages. We found sequence-specific RNA-binding protein and identified its precise binding...
Cell fate commitment is driven by dynamic changes in chromatin architecture and activity of lineage-specific transcription factors (TFs). The assembly factor-1 (CAF-1) a histone chaperone that regulates facilitating nucleosome during DNA replication. Accumulating evidence supports substantial role CAF-1 cell maintenance, but the mechanisms which restricts lineage choice remain poorly understood. Here, we investigate how influences dynamics TF differentiation. We show suppression triggers...
Abstract Ribonuclease (RNase) MRP is a conserved RNA-based enzyme that essential for maturation of ribosomal RNA (rRNA) in eukaryotes. However, the composition and substrate specificity this multisubunit ribonucleoprotein complex higher eukaryotes remain mystery. Here, we identify NEPRO C18ORF21 as constitutive subunits metazoan RNase MRP. Both proteins are specific to only ones distinguishing from closely related P, which selectively cleaves transfer RNA-like substrates. We find each form...
RNA interference (RNAi) is a critical component of many cellular antiviral responses in plants, invertebrates, and mammals. However, its vivo role host protection from the negative-sense virus influenza type A (flu) unclear. Here we have examined RNAi defense to flu by analyzing Argonaute 1 3 double-knockout mice deficient components RNA-induced silencing complex. Compared littermate controls, flu-infected exhibited increased mortality, consistent with more severe alveolitis pneumonitis....
The manipulation of DNA replication and transcription can be harnessed to control cell fate. Central the regulation these DNA-templated processes are histone chaperones, which in turn emerging as fate regulators. Histone chaperones a group proteins with diverse functions that primarily involved escorting histones assemble nucleosomes maintain chromatin landscape. Whether distinct chaperone pathways whether they function using related mechanisms remain unclear. To address this, we performed...
The chemokine receptors CXCR4 and CCR5 are required for HIV-1 to enter cells, the progression of infection AIDS involves a switch in co-receptor usage virus from CXCR4. These therefore make attractive candidates therapeutic intervention, we have investigated silencing their genes by using ribozymes single-stranded antisense RNAs. In present study, demonstrate that depletion mRNAs can be achieved simultaneously human PBMCs (peripheral blood mononuclear cells), cells commonly used replication....