Nucleolar RNA polymerase II drives ribosome biogenesis.

Nature
Karan J AbrahamKarim Mekhail

Abstract

Proteins are manufactured by ribosomes-macromolecular complexes of protein and RNA molecules that are assembled within major nuclear compartments called nucleoli1,2. Existing models suggest that RNA polymerases I and III (Pol I and Pol III) are the only enzymes that directly mediate the expression of the ribosomal RNA (rRNA) components of ribosomes. Here we show, however, that RNA polymerase II (Pol II) inside human nucleoli operates near genes encoding rRNAs to drive their expression. Pol II, assisted by the neurodegeneration-associated enzyme senataxin, generates a shield comprising triplex nucleic acid structures known as R-loops at intergenic spacers flanking nucleolar rRNA genes. The shield prevents Pol I from producing sense intergenic noncoding RNAs (sincRNAs) that can disrupt nucleolar organization and rRNA expression. These disruptive sincRNAs can be unleashed by Pol II inhibition, senataxin loss, Ewing sarcoma or locus-associated R-loop repression through an experimental system involving the proteins RNaseH1, eGFP and dCas9 (which we refer to as 'red laser'). We reveal a nucleolar Pol-II-dependent mechanism that drives ribosome biogenesis, identify disease-associated disruption of nucleoli by noncoding RNAs, and estab...Continue Reading

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Citations

Oct 1, 2020·Scientific Reports·Lauren A ToddKarim Mekhail
Oct 30, 2020·Nucleic Acids Research·Isabela Fraga de AndradeEmery H Bresnick
Dec 16, 2020·Communications Biology·Guillaume Laflamme, Karim Mekhail
Jan 8, 2021·The EMBO Journal·Frédéric ChédinVincent Vanoosthuyse
Jan 28, 2021·Cells·Evgeny SmirnovDušan Cmarko
Jan 10, 2021·International Journal of Molecular Sciences·Eleni G KaliatsiVassiliki Stamatopoulou
Mar 7, 2021·Genes·Luis E Florencio-MartínezSantiago Martínez-Calvillo
Jun 3, 2021·Genes·Konstantin I PanovNadine Hein
Jun 19, 2021·Nature Communications·Shaliny RamachandranEster M Hammond
Jul 17, 2021·Laboratory Investigation; a Journal of Technical Methods and Pathology·Sarah C KammerudRajeev S Samant
May 27, 2021·RNA·Nasiha S AhmedJacob C Schwartz
Jul 27, 2021·DNA Repair·Vincent Spegg, Matthias Altmeyer
Jul 31, 2021·Science·Tomohiro Yamazaki, Tetsuro Hirose
Aug 7, 2021·Journal of Biochemistry·Mitsuhiro YonedaTakashi Ito
Aug 27, 2021·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Qinyu Hao, Kannanganattu V Prasanth
Sep 10, 2021·The FEBS Journal·Tetsuaki Miyake, John C McDermott
Sep 29, 2021·Nucleic Acids Research·Tamara PhanSebastian Iben

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Datasets Mentioned

BETA
M0297S
U13369.1
GSE68847
GSE115731
GL000220.1

Methods Mentioned

BETA
super-resolution microscopy
immunoprecipitation
fluorescence recovery after photobleaching
environmental stress
antisense oligonucleotides
ChIP
immunoprecipitations
electron microscopy
RNA-seq
transfection

Software Mentioned

Bowtie
Leica LAS
Adobe
getGCskewEtc
bedGraph
rRDNA
NIS
Elements AR
Bowtie package aligner
R

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