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Full-Text Articles in Molecular Biology

A Single Mechanism Of Biogenesis, Initiated And Directed By Piwi Proteins, Explains Pirna Production In Most Animals, Phillip D. Zamore, Ildar Gainetdinov, Cansu Colpan, Katharine Cecchini Apr 2018

A Single Mechanism Of Biogenesis, Initiated And Directed By Piwi Proteins, Explains Pirna Production In Most Animals, Phillip D. Zamore, Ildar Gainetdinov, Cansu Colpan, Katharine Cecchini

University of Massachusetts Medical School Faculty Publications

In animals, piRNAs guide PIWI-proteins to silence transposons and regulate gene expression. The mechanisms for making piRNAs have been proposed to differ among cell types, tissues, and animals. Our data instead suggest a single model that explains piRNA production in most animals. piRNAs initiate piRNA production by guiding PIWI proteins to slice precursor transcripts. Next, PIWI proteins direct the stepwise fragmentation of the sliced precursor transcripts, yielding tail-to-head strings of phased pre-piRNAs. Our analyses detect evidence for this piRNA biogenesis strategy across an evolutionarily broad range of animals including humans. Thus, PIWI proteins initiate and sustain piRNA biogenesis by the ...


The Trim-Nhl Protein Nhl-2 Is A Novel Co-Factor Of The Csr-1 And Hrde-1 22g-Rna Pathways, Peter R. Boag, Gregory M. Davis, Shikui Tu, Rhys N. Colson, Joshua W. T. Anderson, Menachem J. Gunzburg, Michelle A. Francisco, Debashish Ray, Tuhin Maity, Monica Z. Wu, Quaid D. Morris, Timothy R. Hughes, Jacqueline A. Wilce, University Of Toronto, Zhiping Weng Feb 2018

The Trim-Nhl Protein Nhl-2 Is A Novel Co-Factor Of The Csr-1 And Hrde-1 22g-Rna Pathways, Peter R. Boag, Gregory M. Davis, Shikui Tu, Rhys N. Colson, Joshua W. T. Anderson, Menachem J. Gunzburg, Michelle A. Francisco, Debashish Ray, Tuhin Maity, Monica Z. Wu, Quaid D. Morris, Timothy R. Hughes, Jacqueline A. Wilce, University Of Toronto, Zhiping Weng

University of Massachusetts Medical School Faculty Publications

Proper regulation of germline gene expression is essential for fertility and maintaining species integrity. In the C. elegans germline, a diverse repertoire of regulatory pathways promote the expression of endogenous germline genes and limit the expression of deleterious transcripts to maintain genome homeostasis. Here we show that the conserved TRIM-NHL protein, NHL-2, plays an essential role in the C. elegans germline, modulating germline chromatin and meiotic chromosome organization. We uncover a role for NHL-2 as a co-factor in both positively (CSR-1) and negatively (HRDE-1) acting germline 22G-small RNA pathways and the somatic nuclear RNAi pathway. Furthermore, we demonstrate that NHL-2 ...


Fundamental Limits On Dynamic Inference From Single Cell Snapshots, Caleb Weinreb, Samuel Wolock, Betsabeh K. Tusi, Merav Socolovsky, Allon M. Klein Aug 2017

Fundamental Limits On Dynamic Inference From Single Cell Snapshots, Caleb Weinreb, Samuel Wolock, Betsabeh K. Tusi, Merav Socolovsky, Allon M. Klein

University of Massachusetts Medical School Faculty Publications

Single cell expression profiling reveals the molecular states of individual cells with unprecedented detail. However, because these methods destroy cells in the process of analysis, they cannot measure how gene expression changes over time. But some information on dynamics is present in the data: the continuum of molecular states in the population can reflect the trajectory of a typical cell. Many methods for extracting single cell dynamics from population data have been proposed. However, all such attempts face a common limitation: for any measured distribution of cell states, there are multiple dynamics that could give rise to it, and by ...


The 4d Nucleome Project, Job Dekker, Andrew S. Belmont, Mitchell Guttman, Victor O. Leshyk, John T. Lis, Stavros Lomvardas, Leonid A. Mirny, Clodagh C. O'Shea, Peter J. Park, Bing Ren, Joan C. Ritland Politz, Jay Shendure, Sheng Zong Jan 2017

The 4d Nucleome Project, Job Dekker, Andrew S. Belmont, Mitchell Guttman, Victor O. Leshyk, John T. Lis, Stavros Lomvardas, Leonid A. Mirny, Clodagh C. O'Shea, Peter J. Park, Bing Ren, Joan C. Ritland Politz, Jay Shendure, Sheng Zong

University of Massachusetts Medical School Faculty Publications

The spatial organization of the genome and its dynamics contribute to gene expression and cellular function in normal development as well as in disease. Although we are increasingly well equipped to determine a genome's sequence and linear chromatin composition, studying the three-dimensional organization of the genome with high spatial and temporal resolution remains challenging. The 4D Nucleome Network aims to develop and apply approaches to map the structure and dynamics of the human and mouse genomes in space and time with the long term goal of gaining deeper mechanistic understanding of how the nucleus is organized. The project will ...