Messenger RNA splicing: Role of small nuclear RNA-protein complexes

1986 ◽  
Vol 21 ◽  
pp. 255-265
Author(s):  
Y Ohshima
1988 ◽  
Vol 16 (6) ◽  
pp. 943-944 ◽  
Author(s):  
JÖRG HAMM ◽  
DANIEL SCHERLY ◽  
IAIN W. MATTAJ

Hepatology ◽  
2015 ◽  
Vol 61 (4) ◽  
pp. 1382-1391 ◽  
Author(s):  
Wendy L. van der Woerd ◽  
Johanna Mulder ◽  
Franco Pagani ◽  
Ulrich Beuers ◽  
Roderick H.J. Houwen ◽  
...  

2020 ◽  
Vol 89 (1) ◽  
pp. 333-358 ◽  
Author(s):  
Ruixue Wan ◽  
Rui Bai ◽  
Xiechao Zhan ◽  
Yigong Shi

Splicing of the precursor messenger RNA, involving intron removal and exon ligation, is mediated by the spliceosome. Together with biochemical and genetic investigations of the past four decades, structural studies of the intact spliceosome at atomic resolution since 2015 have led to mechanistic delineation of RNA splicing with remarkable insights. The spliceosome is proven to be a protein-orchestrated metalloribozyme. Conserved elements of small nuclear RNA (snRNA) constitute the splicing active site with two catalytic metal ions and recognize three conserved intron elements through duplex formation, which are delivered into the splicing active site for branching and exon ligation. The protein components of the spliceosome stabilize the conformation of the snRNA, drive spliceosome remodeling, orchestrate the movement of the RNA elements, and facilitate the splicing reaction. The overall organization of the spliceosome and the configuration of the splicing active site are strictly conserved between human and yeast.


1991 ◽  
Vol 11 (11) ◽  
pp. 5571-5577 ◽  
Author(s):  
S L Yean ◽  
R J Lin

U4 and U6 small nuclear RNAs reside in a single ribonucleoprotein particle, and both are required for pre-mRNA splicing. The U4/U6 and U5 small nuclear ribonucleoproteins join U1 and U2 on the pre-mRNA during spliceosome assembly. Binding of U4 is then destabilized prior to or concomitant with the 5' cleavage-ligation. In order to test the role of U4 RNA, we isolated a functional spliceosome by using extracts prepared from yeast cells carrying a temperature-sensitive allele of prp2 (rna2). The isolated prp2 delta spliceosome contains U2, U5, U6, and possibly also U1 and can be activated to splice the bound pre-mRNA. U4 RNA does not associate with the isolated spliceosomes and is shown not to be involved in the subsequent cleavage-ligation reactions. These results are consistent with the hypothesis that the role of U4 in pre-mRNA splicing is to deliver U6 to the spliceosome.


1991 ◽  
Vol 11 (11) ◽  
pp. 5571-5577
Author(s):  
S L Yean ◽  
R J Lin

U4 and U6 small nuclear RNAs reside in a single ribonucleoprotein particle, and both are required for pre-mRNA splicing. The U4/U6 and U5 small nuclear ribonucleoproteins join U1 and U2 on the pre-mRNA during spliceosome assembly. Binding of U4 is then destabilized prior to or concomitant with the 5' cleavage-ligation. In order to test the role of U4 RNA, we isolated a functional spliceosome by using extracts prepared from yeast cells carrying a temperature-sensitive allele of prp2 (rna2). The isolated prp2 delta spliceosome contains U2, U5, U6, and possibly also U1 and can be activated to splice the bound pre-mRNA. U4 RNA does not associate with the isolated spliceosomes and is shown not to be involved in the subsequent cleavage-ligation reactions. These results are consistent with the hypothesis that the role of U4 in pre-mRNA splicing is to deliver U6 to the spliceosome.


2021 ◽  
Author(s):  
Alisa K. White ◽  
Marybeth Baumgartner ◽  
Madisen F. Lee ◽  
Kyle D. Drake ◽  
Gabriela S. Aquino ◽  
...  

AbstractMutations in minor spliceosome component RNU4ATAC, a small nuclear RNA (snRNA), are linked to primary microcephaly. We have reported that in the conditional knockout (cKO) mice for Rnu11, another minor spliceosome snRNA, minor intron splicing defect in minor intron-containing genes (MIGs) regulating cell cycle resulted in cell cycle defects, with a concomitant increase in γH2aX+ cells and p53-mediated apoptosis. Trp53 ablation in the Rnu11 cKO mice did not prevent microcephaly. However, RNAseq analysis of the double knockout (dKO) pallium reflected transcriptomic shift towards the control from the Rnu11 cKO. We found elevated minor intron retention and alternative splicing across minor introns in the dKO. Disruption of these MIGs resulted in cell cycle defects that were more severe and detected earlier in the dKO, but with delayed detection of γH2aX+ DNA damage. Thus, p53 might also play a role in causing DNA damage in the developing pallium. In all, our findings further refine our understanding of the role of the minor spliceosome in cortical development and identify MIGs underpinning microcephaly in minor spliceosome-related diseases.


Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 332
Author(s):  
Yan Zhao ◽  
Hongling Peng

Epigenetics is identified as the study of heritable modifications in gene expression and regulation that do not involve DNA sequence alterations, such as DNA methylation, histone modifications, etc. Importantly, N6-methyladenosine (m6A) methylation modification is one of the most common epigenetic modifications of eukaryotic messenger RNA (mRNA), which plays a key role in various cellular processes. It can not only mediate various RNA metabolic processes such as RNA splicing, translation, and decay under the catalytic regulation of related enzymes but can also affect the normal development of bone marrow hematopoiesis by regulating the self-renewal, proliferation, and differentiation of pluripotent stem cells in the hematopoietic microenvironment of bone marrow. In recent years, numerous studies have demonstrated that m6A methylation modifications play an important role in the development and progression of hematologic malignancies (e.g., leukemia, lymphoma, myelodysplastic syndromes [MDS], multiple myeloma [MM], etc.). Targeting the inhibition of m6A-associated factors can contribute to increased susceptibility of patients with hematologic malignancies to therapeutic agents. Therefore, this review elaborates on the biological characteristics and normal hematopoietic regulatory functions of m6A methylation modifications and their role in the pathogenesis of hematologic malignancies.


Genes ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 432 ◽  
Author(s):  
Chandran Nithin ◽  
Pritha Ghosh ◽  
Janusz Bujnicki

RNA-protein (RNP) interactions play essential roles in many biological processes, such as regulation of co-transcriptional and post-transcriptional gene expression, RNA splicing, transport, storage and stabilization, as well as protein synthesis. An increasing number of RNP structures would aid in a better understanding of these processes. However, due to the technical difficulties associated with experimental determination of macromolecular structures by high-resolution methods, studies on RNP recognition and complex formation present significant challenges. As an alternative, computational prediction of RNP interactions can be carried out. Structural models obtained by theoretical predictive methods are, in general, less reliable compared to models based on experimental measurements but they can be sufficiently accurate to be used as a basis for to formulating functional hypotheses. In this article, we present an overview of computational methods for 3D structure prediction of RNP complexes. We discuss currently available methods for macromolecular docking and for scoring 3D structural models of RNP complexes in particular. Additionally, we also review benchmarks that have been developed to assess the accuracy of these methods.


Sign in / Sign up

Export Citation Format

Share Document