Andrea J. Kriz
Massachusetts Institute of Technology
Publications 8
#1Anthony C. Chiu (MIT: Massachusetts Institute of Technology)H-Index: 2
#2Hiroshi I. Suzuki (MIT: Massachusetts Institute of Technology)H-Index: 19
Last.Phillip A. Sharp (MIT: Massachusetts Institute of Technology)H-Index: 139
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Summary Regulation of RNA polymerase II (Pol II) elongation is a critical step in gene regulation. Here, we report that U1 snRNP recognition and transcription pausing at stable nucleosomes are linked through premature polyadenylation signal (PAS) termination. By generating RNA exosome conditional deletion mouse embryonic stem cells, we identified a large class of polyadenylated short transcripts in the sense direction destabilized by the RNA exosome. These PAS termination events are enriched at ...
27 CitationsSource
#1F. Ann RanH-Index: 10
#2Le CongH-Index: 16
Last.Feng Zhang (Broad Institute)H-Index: 115
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The physical size of the commonly used Cas9 from Streptococcus pyogenes poses challenges for CRISPR-Cas genome editing systems that use the adeno-associated virus as a delivery vehicle; here, smaller Cas9 orthologues are characterized, and Cas9 from Staphylococcus aureus allowed targeting of the cholesterol regulatory gene Pcsk9 in the mouse liver.
1,051 CitationsSource
#1Xuebing WuH-Index: 20
#2Douglas ScottH-Index: 102
Last.Phillip A. SharpH-Index: 139
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Bacterial type II CRISPR-Cas9 systems have been widely adapted for RNA- guided genome editing and transcription regulation in eukaryotic cells, yet their in vivo target specificity is poorly understood. Here we mapped genome-wide binding sites of a catalytically inactive Cas9 (dCas9) from Streptococcus pyogenes loaded with single guide RNAs (sgRNAs) in mouse embryonic stem cells (mESCs). Each of the four sgRNAs tested targets dCas9 to tens to thousands of genomic sites, characterized by a 5-nucl...
577 CitationsSource
#1Xuebing Wu (MIT: Massachusetts Institute of Technology)H-Index: 20
#2Andrea J. Kriz (MIT: Massachusetts Institute of Technology)H-Index: 5
Last.Phillip A. Sharp (MIT: Massachusetts Institute of Technology)H-Index: 139
view all 3 authors...
The CRISPR-Cas9 system, naturally a defense mechanism in prokaryotes, has been repurposed as an RNA-guided DNA targeting platform. It has been widely used for genome editing and transcriptome modulation, and has shown great promise in correcting mutations in human genetic diseases. Off-target effects are a critical issue for all of these applications. Here we review the current status on the target specificity of the CRISPR-Cas9 system.
117 CitationsSource
#1Xuebing WuH-Index: 20
#2Albert W. ChengH-Index: 28
Last.Daniel B. DadonH-Index: 7
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2 Citations
#1Albert E. AlmadaH-Index: 6
#2Xuebing WuH-Index: 20
Last.Phillip A. SharpH-Index: 139
view all 5 authors...
Asymmetric sequence determinants flanking gene transcription start sites are shown to control directionality of transcription elongation in mammalian cells by regulating promoter-proximal cleavage and polyadenylation.
249 CitationsSource