Functions and mechanisms of spliceosomal small nuclear RNA pseudouridylation

Wu, Guowei; Yu, Andrew T.; Kantartzis, Athena; Yu, Yi‐Tao

doi:10.1002/wrna.77

Cited by 31 publications

(28 citation statements)

References 63 publications

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“…Powerful experimental systems, such as the Xenopus oocyte system and the yeast biochemistry and genetics systems, provided new ways to go about research into this area, and scientists took full advantage [reviewed in (Wu et al, 2011b)]. Now, we are beginning to develop a clearer picture as to how these modified nucleotides, especially pseudouridines, are formed, and what roles they play in the cell.…”

Section: Discovery Of Pseudouridines and Other Modified Nucleotidesmentioning

confidence: 99%

“…Unfortunately, due primarily to the lack of effective assays and experimental systems, functional analysis of pseudouridines in spliceosomal snRNAs (and RNA in general) has proceeded slowly. In the late 1990s, though, several labs developed highly sensitive assays and systems for studying modified nucleotides in RNA, making it possible to dissect the function of pseudouridines in spliceosomal snRNAs during pre-mRNA splicing [reviewed in (Wu et al, 2011b)]. Since U2 contains the most pseudouridines when compared with all other spliceosomal snRNAs (Massenet et al, 1998;Yu et al, 1999), it has been the main focus of functional study.…”

Section: Functions Of Spliceosomal Snrna Pseudouridylationmentioning

confidence: 99%

“…About 15 years ago, though, several laboratories began to turn their attention to the mechanisms and functions of these modifications in spliceosomal snRNAs and rRNAs (Bachellerie et al, 1995;Cavaillé et al, 1996;KissLászló et al, 1996;Tycowski et al, 1996;Ganot et al, 1997;Ni et al, 1997;Smith and Steitz, 1997;Tycowski et al, 1998;Yu et al, 1998;Lowe and Eddy, 1999). Multiple effective assays and systems have since been developed for RNA modification research [reviewed in (Wu et al, 2011b)]. The advent of these assays and systems has helped to accelerate research into RNA modification, leading to some significant developments in this research area.…”

Section: Introductionmentioning

confidence: 99%

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Pseudouridines in spliceosomal snRNAs

2011

Protein Cell

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Spliceosomal RNAs are a family of small nuclear RNAs (snRNAs) that are essential for pre-mRNA splicing. All vertebrate spliceosomal snRNAs are extensively pseudouridylated after transcription. Pseudouridines in spliceosomal snRNAs are generally clustered in regions that are functionally important during splicing. Many of these modified nucleotides are conserved across species lines. Recent studies have demonstrated that spliceosomal snRNA pseudouridylation is catalyzed by two different mechanisms: an RNA-dependent mechanism and an RNA-independent mechanism. The functions of the pseudouridines in spliceosomal snRNAs (U2 snRNA in particular) have also been extensively studied. Experimental data indicate that virtually all pseudouridines in U2 snRNA are functionally important. Besides the currently known pseudouridines (constitutive modifications), recent work has also indicated that pseudouridylation can be induced at novel positions under stress conditions, thus strongly suggesting that pseudouridylation is also a regulatory modification.

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Section: Discovery Of Pseudouridines and Other Modified Nucleotidesmentioning

confidence: 99%

Section: Functions Of Spliceosomal Snrna Pseudouridylationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pseudouridines in spliceosomal snRNAs

2011

Protein Cell

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“…10 The Presence of C in Various RNAs C was first identified in rRNA, 1 (recently reviewed by Ge and Yu 15 ) and tRNA. 1 Further occurrences of C are known in small nuclear RNAs of various eukaryotes, as is reviewed in, e.g., refs 15,41 . As an example, the C in spliceosomal branch site of U2 snRNA will be discussed below in some detail.…”

Section: General Function/structural Aspects Of Cmentioning

confidence: 99%

“…in refs. 15,41 A prominent example is a C residue in eukaryotic U2 RNA that stabilizes and fine-tunes spliceosomal branchsite interaction 39,173 , involving a water-CNH1 hydrogen bond. 174,175 Functional importance for RNA C in artificial mRNAs Synthetic replacement of all uridines by C renders mRNAs non-immunogenic 176 , increases biological stability [176][177][178] and enhances translation in vivo 176,179,180 , while reducing PKR activation.…”

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confidence: 99%

Pseudouridine: Still mysterious, but never a fake (uridine)!

Spenkuch

Motorin

Helm³

2014

RNA Biology

179

186

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Pseudouridine (C) is the most abundant of >150 nucleoside modifications in RNA. Although C was discovered as the first modified nucleoside more than half a century ago, neither the enzymatic mechanism of its formation, nor the function of this modification are fully elucidated. We present the consistent picture of C synthases, their substrates and their substrate positions in model organisms of all domains of life as it has emerged to date and point out the challenges that remain concerning higher eukaryotes and the elucidation of the enzymatic mechanism.

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Non‐m⁶A RNA modifications in haematological malignancies

Chen,

Wang

et al. 2024

Clinical & Translational Med

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Dysregulated RNA modifications, stemming from the aberrant expression and/or malfunction of RNA modification regulators operating through various pathways, play pivotal roles in driving the progression of haematological malignancies. Among RNA modifications, N6‐methyladenosine (m6A) RNA modification, the most abundant internal mRNA modification, stands out as the most extensively studied modification. This prominence underscores the crucial role of the layer of epitranscriptomic regulation in controlling haematopoietic cell fate and therefore the development of haematological malignancies. Additionally, other RNA modifications (non‐m6A RNA modifications) have gained increasing attention for their essential roles in haematological malignancies. Although the roles of the m6A modification machinery in haematopoietic malignancies have been well reviewed thus far, such reviews are lacking for non‐m6A RNA modifications. In this review, we mainly focus on the roles and implications of non‐m6A RNA modifications, including N4‐acetylcytidine, pseudouridylation, 5‐methylcytosine, adenosine to inosine editing, 2′‐O‐methylation, N1‐methyladenosine and N7‐methylguanosine in haematopoietic malignancies. We summarise the regulatory enzymes and cellular functions of non‐m6A RNA modifications, followed by the discussions of the recent studies on the biological roles and underlying mechanisms of non‐m6A RNA modifications in haematological malignancies. We also highlight the potential of therapeutically targeting dysregulated non‐m6A modifiers in blood cancer.

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Functions and mechanisms of spliceosomal small nuclear RNA pseudouridylation

Cited by 31 publications

References 63 publications

Pseudouridines in spliceosomal snRNAs

Pseudouridines in spliceosomal snRNAs

Pseudouridine: Still mysterious, but never a fake (uridine)!

Non‐m⁶A RNA modifications in haematological malignancies

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Functions and mechanisms of spliceosomal small nuclear RNA pseudouridylation

Cited by 31 publications

References 63 publications

Pseudouridines in spliceosomal snRNAs

Pseudouridines in spliceosomal snRNAs

Pseudouridine: Still mysterious, but never a fake (uridine)!

Non‐m6A RNA modifications in haematological malignancies

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Non‐m⁶A RNA modifications in haematological malignancies