PAF Complex Plays Novel Subunit-Specific Roles in Alternative Cleavage and Polyadenylation

PLoS Genetics
Yan YangBrian D Dynlacht

Abstract

The PAF complex (Paf1C) has been shown to regulate chromatin modifications, gene transcription, and RNA polymerase II (PolII) elongation. Here, we provide the first genome-wide profiles for the distribution of the entire complex in mammalian cells using chromatin immunoprecipitation and high throughput sequencing. We show that Paf1C is recruited not only to promoters and gene bodies, but also to regions downstream of cleavage/polyadenylation (pA) sites at 3' ends, a profile that sharply contrasted with the yeast complex. Remarkably, we identified novel, subunit-specific links between Paf1C and regulation of alternative cleavage and polyadenylation (APA) and upstream antisense transcription using RNAi coupled with deep sequencing of the 3' ends of transcripts. Moreover, we found that depletion of Paf1C subunits resulted in the accumulation of PolII over gene bodies, which coincided with APA. Depletion of specific Paf1C subunits led to global loss of histone H2B ubiquitylation, although there was little impact of Paf1C depletion on other histone modifications, including tri-methylation of histone H3 on lysines 4 and 36 (H3K4me3 and H3K36me3), previously associated with this complex. Our results provide surprising differences with...Continue Reading

References

Mar 9, 2002·Molecular and Cellular Biology·Cherie L Mueller, Judith A Jaehning
Sep 21, 2002·Molecular and Cellular Biology·Nevan J KroganJack F Greenblatt
Jan 6, 2005·Molecular and Cellular Biology·Orit Rozenblatt-RosenMatthew Meyerson
Jan 14, 2005·Nucleic Acids Research·Bin TianCarol S Lutz
Oct 26, 2005·Molecular Cell·Kathryn E SheldonKaren M Arndt
Dec 16, 2005·Molecular and Cellular Biology·Karen AdelmanJohn T Lis
Dec 25, 2007·Nature Structural & Molecular Biology·Kira Glover-CutterDavid L Bentley
Dec 26, 2007·Cellular and Molecular Life Sciences : CMLS·C R MandelL Tong
Jan 13, 2009·Proceedings of the National Academy of Sciences of the United States of America·Orit Rozenblatt-RosenMatthew Meyerson
Jan 12, 2010·Biochimica Et Biophysica Acta·Judith A Jaehning
May 4, 2010·Cell·Peter B RahlRichard A Young
Jun 15, 2010·Cancer Cell·Nancy A Speck, Christopher R Vakoc
Sep 8, 2010·Nature Structural & Molecular Biology·Andreas MayerPatrick Cramer
Oct 1, 2010·Nature·Daisuke KaidaGideon Dreyfuss
Feb 1, 2011·Wiley Interdisciplinary Reviews. RNA·Carol S Lutz, Alexandra Moreira
Feb 19, 2011·Molecular Cell·Takashi NagaikeJames L Manley
Feb 23, 2011·Developmental Biology·Adam D LangenbacherJau-Nian Chen
May 10, 2011·Proceedings of the National Academy of Sciences of the United States of America·Patrik AspBrian David Dynlacht
May 24, 2011·The EMBO Journal·Pedro A B PintoAlexandra Moreira
Aug 30, 2011·Proceedings of the National Academy of Sciences of the United States of America·Nanhai HeQiang Zhou
Sep 24, 2011·RNA Biology·Takashi Nagaike, James L Manley
Oct 1, 2011·Wiley Interdisciplinary Reviews. RNA·Carol S Lutz, Alexandra Moreira
Jan 19, 2012·Molecular and Cellular Biology·Vasupradha VethanthamBrian D Dynlacht
Jul 10, 2012·Cell·Michael G BergGideon Dreyfuss
Jul 10, 2012·Nucleic Acids Research·Eleonora de KlerkPeter A C 't Hoen
Mar 19, 2013·The EMBO Journal·A Hongjun WangVittorio Sartorelli
May 2, 2013·Trends in Biochemical Sciences·Bin Tian, James L Manley

❮ Previous
Next ❯

Citations

May 12, 2016·European Journal of Human Genetics : EJHG·Matthew A M ToddDavid J Picketts
Apr 30, 2017·RNA Biology·Jonathan NeveAndré Martin Furger
Dec 23, 2016·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Françoise S HoweJane Mellor
Nov 30, 2018·Nature·Sara J DubburyPhillip A Sharp
Sep 2, 2017·Science·Fei Xavier ChenAli Shilatifard
Mar 5, 2020·Wiley Interdisciplinary Reviews. RNA·Michael TellierShona Murphy
Jun 30, 2019·Proceedings of the National Academy of Sciences of the United States of America·Liming HouBrian David Dynlacht
Sep 16, 2017·Nucleic Acids Research·Chunliu HuangChengguo Yao
Nov 4, 2016·Nature Reviews. Molecular Cell Biology·Bin Tian, James L Manley
Nov 20, 2020·Nature Reviews. Molecular Cell Biology·Melvin Noe GonzalezJesper Q Svejstrup
Dec 10, 2020·Viruses·Iván Gabriel PerosPablo Daniel Ghiringhelli
Dec 31, 2020·Life Science Alliance·Li DingFrank Buchholz
Apr 13, 2021·Wiley Interdisciplinary Reviews. RNA·Isabel Pereira-Castro, Alexandra Moreira
Jul 1, 2019·Genetics·Mitchell A EllisonKaren M Arndt
Jun 20, 2021·Molecular Cell·Kristina ŽumerPatrick Cramer
Aug 24, 2021·PloS One·Anne E RoehrigPablo Rodriguez-Viciana

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE72574
GSE44119
GSE34960
GSE25308

Methods Mentioned

BETA
ubiquitination
Co-immunoprecipitation
immunoprecipitation
ChIP
ChIP-seq
RNA-seq
PCR
transfection
cDNA

Software Mentioned

READS
bedGraphToBigWig
bowtie2
qChIP
GAAP
Integrative Genomics Browser ( IGB )
house
Global Analysis of Alternative Polyadenylation ( GAAP

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.