Evidence map›Paper›PMID 27766492›Full record

ArticleJournal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry2016

CO and NO bind to Fe(II) DiGeorge critical region 8 heme but do not restore primary microRNA processing activity.

Judy P Hines, Aaron T Smith, Jose P Jacob, Gudrun S Lukat-Rodgers, Ian Barr, Kenton R Rodgers, Feng Guo, Judith N Burstyn

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Article in Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Gas-sensing riboceptors.RNA biology · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Judy P HinesDepartment of Chemistry, University of Wisconsin-Madison, 1101 University Ave., Madison, WI, 53706-1322, USA.
Aaron T SmithDepartment of Chemistry and Biochemistry, University of Maryland, Baltimore County, Baltimore, MD, 21250-0001, USA.
Jose P JacobDepartment of Biological Chemistry, David Geffen School of Medicine, Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, 90095-3075, USA.
Gudrun S Lukat-RodgersDepartment of Chemistry and Molecular Biology, North Dakota State University, Fargo, ND, 58108-6050, USA.
Ian BarrDepartment of Biological Chemistry, David Geffen School of Medicine, Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, 90095-3075, USA.
Kenton R RodgersDepartment of Chemistry and Molecular Biology, North Dakota State University, Fargo, ND, 58108-6050, USA.
Feng GuoDepartment of Biological Chemistry, David Geffen School of Medicine, Molecular Biology Institute, University of California Los Angeles, Los Angeles, CA, 90095-3075, USA.
Judith N BurstynDepartment of Chemistry, University of Wisconsin-Madison, 1101 University Ave., Madison, WI, 53706-1322, USA. burstyn@chem.wisc.edu.

Funding

Molecular recognition and regulation in microRNA processing by the DGCR8 proteinR01GM080563 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GUO, FENG · 2007 to 2011
$1.3M
Determining the structural basis for the mechanism of catalytic O2 evolution by tR15GM094039 · NIGMS · NORTH DAKOTA STATE UNIVERSITY · PI LUKAT-RODGERS, GUDRUN SUSANNE · 2010 to 2010
$431k
NIGMS NIH HHS R01 GM080563NIGMS NIH HHS R15 GM094039
6 · The paper itself

Abstract

The RNA-binding heme protein DiGeorge critical region 8 (DGCR8) and its ribonuclease partner Drosha cleave primary transcripts of microRNA (pri-miRNA) as part of the canonical microRNA (miRNA) processing pathway. Previous studies show that bis-cysteine thiolate-coordinated Fe(III) DGCR8 supports pri-miRNA processing activity, while Fe(II) DGCR8 does not. In this study, we further characterized Fe(II) DGCR8 and tested whether CO or NO might bind and restore pri-miRNA processing activity to the reduced protein. Fe(II) DGCR8 RNA-binding heme domain (Rhed) undergoes a pH-dependent transition from 6-coordinate to 5-coordinate, due to protonation and loss of a lysine ligand; the ligand bound throughout the pH change is a histidine. Fe(II) Rhed binds CO and NO from 6- and 5-coordinate states, forming common CO and NO adducts at all pHs. Fe(II)-CO Rhed is 6-coordinate, low-spin, and pH insensitive with the histidine ligand retained, suggesting that the protonatable lysine ligand has been replaced by CO. Fe(II)-NO Rhed is 5-coordinate and pH insensitive. Fe(II)-NO also forms slowly upon reaction of Fe(III) Rhed with excess NO via a stepwise process. Heme reduction by NO is rate-limiting, and the rate would be negligible at physiological NO concentrations. Importantly, in vitro pri-miRNA processing assays show that both CO- and NO-bound DGCR8 species are inactive. Fe(II), Fe(II)-CO, and Fe(II)-NO Rhed do not bear either of the cysteine ligands found in the Fe(III) state. These data support a model in which the bis-cysteine thiolate ligand environment of Fe(III) DGCR8 is necessary for establishing proper pri-miRNA binding and enabling processing activity.

Indexed as

Binding SitesCarbon MonoxideCircular DichroismCysteineFerric CompoundsFerrous CompoundsHemeHistidineHumansHydrogen-Ion ConcentrationLigandsLysineMicroRNAsModels, BiologicalNitric OxideProtein BindingCarbon MonoxideCysteinecysteine thiolateDGCR8 protein, humanFerric CompoundsFerrous CompoundsHemeHistidineLigandsLysineMicroRNAsNitric OxideRNA-Binding ProteinsCarbon monoxideHememicroRNANitric oxideRNA processing

Identifiers

PMID27766492

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.