CryoEM structures of pseudouridine-free ribosome suggest impacts of chemical modifications on ribosome conformations

Zhao, Yu; Rai, Jay; Yu, Hong-Guo; Li, Hong

doi:10.1016/j.str.2022.04.002

Cited by 21 publications

(24 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…S28B ) ( 10 ). Second, while chemical modifications can result in additional stabilization of the ribosome, complete ribosomes can be formed even in the presence of catalytically dead enzymes involved in pseudouridylation while the conformational freedom of subunits including inter-subunit rotation is partially affected ( 72 ). Third, the heterogeneity of chemical modifications as observed in the human ribosome ( 73 ) can be explained as the result of several redundant sites of chemical modifications that together guarantee efficient ribosome assembly without the need for selective and quantitative modification.…”

Section: Discussionmentioning

confidence: 99%

Principles of human pre-60Sbiogenesis

Broeck

Klinge

2023

Preprint

View full text Add to dashboard Cite

During early stages of human large ribosomal subunit (60S) biogenesis, an ensemble of assembly factors establishes and fine-tunes the essential RNA functional centers of pre-60Sparticles by an unknown mechanism. Here, we report a series of cryo-electron microscopy structures of human nucleolar and nuclear pre-60Sassembly intermediates at resolutions of 2.5-3.2 angstroms. These structures show how protein interaction hubs tether assembly factor complexes to nucleolar particles and how GTPases and ATPases couple irreversible nucleotide hydrolysis steps to the installation of functional centers. Nuclear stages highlight how a conserved RNA processing complex, the rixosome, couples large-scale RNA conformational changes to pre-rRNA processing by the RNA degradation machinery. Our ensemble of human pre-60Sparticles provides a rich foundation to elucidate the molecular principles of ribosome formation.

show abstract

Section: Discussionmentioning

confidence: 99%

Principles of human pre-60Sbiogenesis

Broeck

Klinge

2023

Preprint

View full text Add to dashboard Cite

show abstract

“…S29B) ( 10 ). Second, although chemical modifications can result in additional stabilization of the ribosome, complete ribosomes can be formed even in the presence of catalytically dead enzymes involved in pseudouridylation while the conformational freedom of subunits including intersubunit rotation is partially affected ( 68 ). Third, the heterogeneity of chemical modifications as observed in the human ribosome ( 69 ) can be explained as the result of several redundant sites of chemical modifications that together guarantee efficient ribosome assembly without the need for selective and quantitative modification.…”

Section: Discussionmentioning

confidence: 99%

Principles of human pre-60 S biogenesis

Broeck

Klinge

2023

Science

View full text Add to dashboard Cite

During the early stages of human large ribosomal subunit (60 S ) biogenesis, an ensemble of assembly factors establishes and fine-tunes the essential RNA functional centers of pre-60 S particles by an unknown mechanism. Here, we report a series of cryo–electron microscopy structures of human nucleolar and nuclear pre-60 S assembly intermediates at resolutions of 2.5 to 3.2 angstroms. These structures show how protein interaction hubs tether assembly factor complexes to nucleolar particles and how guanosine triphosphatases and adenosine triphosphatase couple irreversible nucleotide hydrolysis steps to the installation of functional centers. Nuclear stages highlight how a conserved RNA-processing complex, the rixosome, couples large-scale RNA conformational changes with pre–ribosomal RNA processing by the RNA degradation machinery. Our ensemble of human pre-60 S particles provides a rich foundation with which to elucidate the molecular principles of ribosome formation.

show abstract

“…Modification of uridine to pseudoU stiffens the RNA backbone, usually resulting in more stable RNA structure, but the impact on structure is dependent on the context of the pseudoU modification [ 140 ]. Lack of pseudoU modification is associated with altered structural dynamics in the ribosome, specifically in the way the sections of the ribosome rotate with respect to one another [ 141 ]. The ability of pseudoU to change the structure of the ribosome and modulate its dynamics probably contributes to the translational defect in cells with ribosomes that lack pseudoU [ 141 ].…”

Section: Mechanisms Underlying Structural Recognition and Dynamicsmentioning

confidence: 99%

“…Lack of pseudoU modification is associated with altered structural dynamics in the ribosome, specifically in the way the sections of the ribosome rotate with respect to one another [ 141 ]. The ability of pseudoU to change the structure of the ribosome and modulate its dynamics probably contributes to the translational defect in cells with ribosomes that lack pseudoU [ 141 ]. Although modifications are the rule for noncoding RNAs such as ribosomal RNA and tRNAs, RNA modifications are also present in pre-processed mRNAs, reviewed in [ 137 ].…”

Section: Mechanisms Underlying Structural Recognition and Dynamicsmentioning

confidence: 99%

How does precursor RNA structure influence RNA processing and gene expression?

2023

View full text Add to dashboard Cite

RNA is a fundamental biomolecule that has many purposes within cells. Due to its single-stranded and flexible nature, RNA naturally folds into complex and dynamic structures. Recent technological and computational advances have produced an explosion of RNA structural data. Many RNA structures clearly have regulatory and functional properties. Studying the structure of nascent RNAs is particularly challenging due to their low abundance and long length, but their structures are important because they can influence RNA processing. Precursor RNA processing is a nexus of pathways that determines mature isoform composition and that controls gene expression. In this review, we examine what is known about human nascent RNA structure and the influence of RNA structure on processing of precursor RNAs. These known structures provide examples of how other nascent RNAs may be structured and show how novel RNA structures may influence RNA processing including splicing and polyadenylation. RNA structures can be targeted therapeutically to treat disease.

show abstract

CryoEM structures of pseudouridine-free ribosome suggest impacts of chemical modifications on ribosome conformations

Cited by 21 publications

References 79 publications

Principles of human pre-60Sbiogenesis

Principles of human pre-60Sbiogenesis

Principles of human pre-60 S biogenesis

How does precursor RNA structure influence RNA processing and gene expression?

Contact Info

Product

Resources

About