Cutting in-line with iron: ribosomal function and non-oxidative RNA cleavage

Abstract Divalent metal cations are essential to the structure and function of the ribosome. Previous characterizations of the ribosome performed under standard laboratory conditions have implicated Mg2+ as a primary mediator of ribosomal structure and function. Possible contributions of Fe2+ as a ribosomal cofactor have been largely overlooked, despite the ribosome's early evolution in a high Fe2+ environment, and the continued use of Fe2+ by obligate anaerobes inhabiting high Fe2+ niches. Here, we show that (i) Fe2+ cleaves RNA by in-line cleavage, a non-oxidative mechanism that has not previously been shown experimentally for this metal, (ii) the first-order in-line rate constant with respect to divalent cations is >200 times greater with Fe2+ than with Mg2+, (iii) functional ribosomes are associated with Fe2+ after purification from cells grown under low O2 and high Fe2+ and (iv) a small fraction of Fe2+ that is associated with the ribosome is not exchangeable with surrounding divalent cations, presumably because those ions are tightly coordinated by rRNA and deeply buried in the ribosome. In total, these results expand the ancient role of iron in biochemistry and highlight a possible new mechanism of iron toxicity.

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Cutting in-line with iron: ribosomal function and non-oxidative RNA cleavage

10.1101/851097 ◽

2019 ◽

Cited By ~ 2

Author(s):

Rebecca Guth-Metzler ◽

Marcus S. Bray ◽

Moran Frenkel-Pinter ◽

Suttipong Suttapitugsakul ◽

Claudia Montllor-Albalate ◽

...

Keyword(s):

Divalent Cations ◽

Order Rate Constant ◽

Structure And Function ◽

List Type ◽

First Order ◽

Key Points ◽

Ribosomal Function ◽

Continued Use ◽

And Function

AbstractDivalent metal cations are essential to the structure and function of the ribosome. Previous characterizations of the ribosome performed under standard laboratory conditions have implicated Mg2+ as a primary mediator of ribosomal structure and function. Possible contributions of Fe2+ as a ribosomal cofactor have been largely overlooked, despite the ribosome’s early evolution in a high Fe2+ environment, and its continued use by obligate anaerobes inhabiting high Fe2+ niches. Here we show that (i) Fe2+ cleaves RNA by in-line cleavage, a non-oxidative mechanism that has not previously been shown experimentally for this metal, (ii) the first-order rate constant with respect to divalent cations is more than 200 times greater with Fe2+ than with Mg2+, (iii) functional ribosomes are associated with Fe2+ after purification from cells grown under low O2 and high Fe2+, and (iv) a small fraction of Fe2+ that is associated with the ribosome is not exchangeable with surrounding divalent cations, presumably because it is tightly coordinated by rRNA and buried in the ribosome. In total, these results expand the ancient role of iron in biochemistry and highlight a possible new mechanism of iron toxicity.Key PointsFe2+ cleaves rRNA by a non-oxidative in-line cleavage mechanism that is more than 200 times faster than in-line cleavage with Mg2+;ribosomes purified from cells grown under low O2 and high Fe2+ retain ~10 Fe2+ ions per ribosome and produce as much protein as low O2, high Mg2+-grown ribosomes;a small fraction (~2%) of Fe2+ that is associated with the ribosome is not exchangeable.

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The role of divalent cations in structure and function of murine adenosine deaminase

Protein Science ◽

10.1002/pro.5560060509 ◽

1997 ◽

Vol 6 (5) ◽

pp. 1031-1037 ◽

Cited By ~ 29

Author(s):

Bruce F. Cooper ◽

Vera Sideraki ◽

David K. Wilson ◽

David Y. Dominguez ◽

Sandra W. Clark ◽

...

Keyword(s):

Adenosine Deaminase ◽

Divalent Cations ◽

Structure And Function ◽

And Function

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Faculty Opinions recommendation of Critical role of cyclophilin A and its prolyl-peptidyl isomerase activity in the structure and function of the hepatitis C virus replication complex.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1162955.623591 ◽

2009 ◽

Author(s):

Teresa Compton

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

Virus Replication ◽

Critical Role ◽

Cyclophilin A ◽

Structure And Function ◽

Replication Complex ◽

Isomerase Activity ◽

And Function

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Essential Role of Septin 7 in Skeletal Muscle Structure and Function

Biophysical Journal ◽

10.1016/j.bpj.2019.11.1500 ◽

2020 ◽

Vol 118 (3) ◽

pp. 258a

Author(s):

Laszlo Csernoch ◽

Mónika Gönczi ◽

Zsolt Ráduly ◽

László Szabó ◽

Nóra Dobrosi ◽

...

Keyword(s):

Skeletal Muscle ◽

Essential Role ◽

Structure And Function ◽

Muscle Structure ◽

And Function

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Effects of Dysbiosis and Dietary Manipulation on the Digestive Microbiota of a Detritivorous Arthropod

Microorganisms ◽

10.3390/microorganisms9010148 ◽

2021 ◽

Vol 9 (1) ◽

pp. 148

Author(s):

Marius Bredon ◽

Elisabeth Depuydt ◽

Lucas Brisson ◽

Laurent Moulin ◽

Ciriac Charles ◽

...

Keyword(s):

Crucial Role ◽

Structure And Function ◽

Ecological Interactions ◽

Dietary Manipulation ◽

Biotic Factors ◽

Abiotic And Biotic Factors ◽

And Function ◽

Multicellular Organisms ◽

Over Time

The crucial role of microbes in the evolution, development, health, and ecological interactions of multicellular organisms is now widely recognized in the holobiont concept. However, the structure and stability of microbiota are highly dependent on abiotic and biotic factors, especially in the gut, which can be colonized by transient bacteria depending on the host’s diet. We studied these impacts by manipulating the digestive microbiota of the detritivore Armadillidium vulgare and analyzing the consequences on its structure and function. Hosts were exposed to initial starvation and then were fed diets that varied the different components of lignocellulose. A total of 72 digestive microbiota were analyzed according to the type of the diet (standard or enriched in cellulose, lignin, or hemicellulose) and the period following dysbiosis. The results showed that microbiota from the hepatopancreas were very stable and resilient, while the most diverse and labile over time were found in the hindgut. Dysbiosis and selective diets may have affected the host fitness by altering the structure of the microbiota and its predicted functions. Overall, these modifications can therefore have effects not only on the holobiont, but also on the “eco-holobiont” conceptualization of macroorganisms.

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Neuroplacentology in congenital heart disease: placental connections to neurodevelopmental outcomes

Pediatric Research ◽

10.1038/s41390-021-01521-7 ◽

2021 ◽

Author(s):

Rachel L. Leon ◽

Imran N. Mir ◽

Christina L. Herrera ◽

Kavita Sharma ◽

Catherine Y. Spong ◽

...

Keyword(s):

Brain Development ◽

Congenital Heart ◽

Fetal Brain ◽

In Utero ◽

Structure And Function ◽

Brain Growth ◽

Neurodevelopmental Outcomes ◽

Fetal Brain Development ◽

And Function

Abstract Children with congenital heart disease (CHD) are living longer due to effective medical and surgical management. However, the majority have neurodevelopmental delays or disorders. The role of the placenta in fetal brain development is unclear and is the focus of an emerging field known as neuroplacentology. In this review, we summarize neurodevelopmental outcomes in CHD and their brain imaging correlates both in utero and postnatally. We review differences in the structure and function of the placenta in pregnancies complicated by fetal CHD and introduce the concept of a placental inefficiency phenotype that occurs in severe forms of fetal CHD, characterized by a myriad of pathologies. We propose that in CHD placental dysfunction contributes to decreased fetal cerebral oxygen delivery resulting in poor brain growth, brain abnormalities, and impaired neurodevelopment. We conclude the review with key areas for future research in neuroplacentology in the fetal CHD population, including (1) differences in structure and function of the CHD placenta, (2) modifiable and nonmodifiable factors that impact the hemodynamic balance between placental and cerebral circulations, (3) interventions to improve placental function and protect brain development in utero, and (4) the role of genetic and epigenetic influences on the placenta–heart–brain connection. Impact Neuroplacentology seeks to understand placental connections to fetal brain development. In fetuses with CHD, brain growth abnormalities begin in utero. Placental microstructure as well as perfusion and function are abnormal in fetal CHD.

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Endogenous Mammalian Cardiotonic Steroids—A New Cardiovascular Risk Factor?—A Mini-Review

Life ◽

10.3390/life11080727 ◽

2021 ◽

Vol 11 (8) ◽

pp. 727

Author(s):

Natalia Słabiak-Błaż ◽

Grzegorz Piecha

Keyword(s):

Adenosine Triphosphatase ◽

Therapeutic Strategies ◽

Structure And Function ◽

Sodium Potassium ◽

Sodium Homeostasis ◽

Cardiovascular Tissue ◽

Ancient Times ◽

And Function ◽

Regulation Of Blood Pressure

The role of endogenous mammalian cardiotonic steroids (CTS) in the physiology and pathophysiology of the cardiovascular system and the kidneys has interested researchers for more than 20 years. Cardiotonic steroids extracted from toads or plants, such as digitalis, have been used to treat heart disease since ancient times. CTS, also called endogenous digitalis-like factors, take part in the regulation of blood pressure and sodium homeostasis through their effects on the transport enzyme called sodium–potassium adenosine triphosphatase (Na/K-ATPase) in renal and cardiovascular tissue. In recent years, there has been increasing evidence showing deleterious effects of CTS on the structure and function of the heart, vasculature and kidneys. Understanding the role of CTS may be useful in the development of potential new therapeutic strategies.

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The role of GABAA receptor biogenesis, structure and function in epilepsy

Biochemical Society Transactions ◽

10.1042/bst0340863 ◽

2006 ◽

Vol 34 (5) ◽

pp. 863-867 ◽

Cited By ~ 14

Author(s):

S. Mizielinska ◽

S. Greenwood ◽

C.N. Connolly

Keyword(s):

Gabaa Receptor ◽

Structure And Function ◽

Inhibitory Synapses ◽

Normal Brain ◽

Synaptic Targeting ◽

Acid Type ◽

Normal Brain Function ◽

And Function ◽

The Brain

Maintaining the correct balance in neuronal activation is of paramount importance to normal brain function. Imbalances due to changes in excitation or inhibition can lead to a variety of disorders ranging from the clinically extreme (e.g. epilepsy) to the more subtle (e.g. anxiety). In the brain, the most common inhibitory synapses are regulated by GABAA (γ-aminobutyric acid type A) receptors, a role commensurate with their importance as therapeutic targets. Remarkably, we still know relatively little about GABAA receptor biogenesis. Receptors are constructed as pentameric ion channels, with α and β subunits being the minimal requirement, and the incorporation of a γ subunit being necessary for benzodiazepine modulation and synaptic targeting. Insights have been provided by the discovery of several specific assembly signals within different GABAA receptor subunits. Moreover, a number of recent studies on GABAA receptor mutations associated with epilepsy have further enhanced our understanding of GABAA receptor biogenesis, structure and function.

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