scholarly journals Invariant U2 RNA sequences bordering the branchpoint recognition region are essential for interaction with yeast SF3a and SF3b subunits.

1996 ◽  
Vol 16 (3) ◽  
pp. 818-828 ◽  
Author(s):  
D Yan ◽  
M Ares
Keyword(s):  
Yeast Cells ◽  
Small Nuclear Rna ◽  
Recognition Sequence ◽  
Rna Sequences ◽  
Synthetic Lethal ◽  
U2 Snrna ◽  
U6 Snrna ◽  
Synthetic Lethal Interactions ◽  
Protein Components ◽  
And Function

U2 small nuclear RNA (snRNA) contains a sequence (GUAGUA) that pairs with the intron branchpoint during splicing. This sequence is contained within a longer invariant sequence of unknown secondary structure and function that extends between U2 and I and stem IIa. A part of this region has been proposed to pair with U6 in a structure called helix III. We made mutations to test the function of these nucleotides in yeast U2 snRNA. Most single base changes cause no obvious growth defects; however, several single and double mutations are lethal or conditional lethal and cause a block before the first step of splicing. We used U6 compensatory mutations to assess the contribution of helix III and found that if it forms, helix III is dispensable for splicing in Saccharomyces cerevisiae. On the other hand, mutations in known protein components of the splicing apparatus suppress or enhance the phenotypes of mutations within the invariant sequence that connect the branchpoint recognition sequence to stem IIa. Lethal mutations in the region are suppressed by Cus1-54p, a mutant yeast splicing factor homologous to a mammalian SF3b subunit. Synthetic lethal interactions show that this region collaborates with the DEAD-box protein Prp5p and the yeast SF3a subunits Prp9p, Prp11p, and Prp21p. Together, the data show that the highly conserved RNA element downstream of the branchpoint recognition sequence of U2 snRNA in yeast cells functions primarily with the proteins that make up SF3 rather than with U6 snRNA.

An mRNA-type intron is present in the Rhodotorula hasegawae U2 small nuclear RNA gene

1993 ◽  
Vol 13 (9) ◽  
pp. 5613-5619
Author(s):  
Y Takahashi ◽  
S Urushiyama ◽  
T Tani ◽  
Y Ohshima
Keyword(s):  
Mrna Splicing ◽  
Small Nuclear Rna ◽  
U2 Snrna ◽  
U6 Snrna ◽  
Branch Site ◽  
Snrna Gene ◽  
Nuclear Rna ◽  
Catalytic Role ◽  
Mrna Precursor ◽  
Site Recognition

Splicing an mRNA precursor requires multiple factors involving five small nuclear RNA (snRNA) species called U1, U2, U4, U5, and U6. The presence of mRNA-type introns in the U6 snRNA genes of some yeasts led to the hypothesis that U6 snRNA may play a catalytic role in pre-mRNA splicing and that the U6 introns occurred through reverse splicing of an intron from an mRNA precursor into a catalytic site of U6 snRNA. We characterized the U2 snRNA gene of the yeast Rhodotorula hasegawae, which has four mRNA-type introns in the U6 snRNA gene, and found an mRNA-type intron of 60 bp. The intron of the U2 snRNA gene is present in the highly conserved region immediately downstream of the branch site recognition domain. Interestingly, we found that this region can form a novel base pairing with U6 snRNA. We discuss the possible implications of these findings for the mechanisms of intron acquisition and for the role of U2 snRNA in pre-mRNA splicing.

Secondary structure of U6 small nuclear RNA: implications for spliceosome assembly

2010 ◽  
Vol 38 (4) ◽  
pp. 1099-1104 ◽  
Author(s):  
Elizabeth A. Dunn ◽  
Stephen D. Rader
Keyword(s):  
Secondary Structure ◽  
Small Nuclear Rna ◽  
Stem Loop ◽  
New Model ◽  
Rna Molecules ◽  
U6 Snrna ◽  
Small Nuclear Ribonucleoprotein ◽  
Nuclear Rna ◽  
High Level ◽  
And Function

U6 snRNA (small nuclear RNA), one of five RNA molecules that are required for the essential process of pre-mRNA splicing, is notable for its high level of sequence conservation and the important role it is thought to play in the splicing reaction. Nevertheless, the secondary structure of U6 in the free snRNP (small nuclear ribonucleoprotein) form has remained elusive, with predictions changing substantially over the years. In the present review we discuss the evidence for existing models and critically evaluate a fundamental assumption of these models, namely whether the important 3′ ISL (3′ internal stem–loop) is present in the free U6 particle, as well as in the active splicing complex. We compare existing models of free U6 with a newly proposed model lacking the 3′ ISL and evaluate the implications of the new model for the structure and function of U6's base-pairing partner U4 snRNA. Intriguingly, the new model predicts a role for U4 that was unanticipated previously, namely as an activator of U6 for assembly into the splicing machinery.

scholarly journals An mRNA-type intron is present in the Rhodotorula hasegawae U2 small nuclear RNA gene.

1993 ◽  
Vol 13 (9) ◽  
pp. 5613-5619 ◽  
Author(s):  
Y Takahashi ◽  
S Urushiyama ◽  
T Tani ◽  
Y Ohshima
Keyword(s):  
Mrna Splicing ◽  
Small Nuclear Rna ◽  
U2 Snrna ◽  
U6 Snrna ◽  
Branch Site ◽  
Snrna Gene ◽  
Nuclear Rna ◽  
Catalytic Role ◽  
Mrna Precursor ◽  
Site Recognition

Splicing an mRNA precursor requires multiple factors involving five small nuclear RNA (snRNA) species called U1, U2, U4, U5, and U6. The presence of mRNA-type introns in the U6 snRNA genes of some yeasts led to the hypothesis that U6 snRNA may play a catalytic role in pre-mRNA splicing and that the U6 introns occurred through reverse splicing of an intron from an mRNA precursor into a catalytic site of U6 snRNA. We characterized the U2 snRNA gene of the yeast Rhodotorula hasegawae, which has four mRNA-type introns in the U6 snRNA gene, and found an mRNA-type intron of 60 bp. The intron of the U2 snRNA gene is present in the highly conserved region immediately downstream of the branch site recognition domain. Interestingly, we found that this region can form a novel base pairing with U6 snRNA. We discuss the possible implications of these findings for the mechanisms of intron acquisition and for the role of U2 snRNA in pre-mRNA splicing.

scholarly journals Transient Nucleolar Localization Of U6 Small Nuclear RNA InXenopus Laevis Oocytes

2000 ◽  
Vol 11 (7) ◽  
pp. 2419-2428 ◽  
Author(s):  
Thilo Sascha Lange ◽  
Susan A. Gerbi
Keyword(s):  
Nucleolar Localization ◽  
Xenopus Laevis Oocytes ◽  
Small Nuclear Rna ◽  
U2 Snrna ◽  
U6 Snrna ◽  
Nuclear Rna ◽  
Inxenopus Laevis ◽  
Nucleolar Staining ◽  
Over Time

Recent studies on the 2′-O-methylation and pseudouridylation of U6 small nuclear RNA (snRNA) hypothesize that these posttranscriptional modifications might occur in the nucleolus. In this report, we present direct evidence for the nucleolar localization of U6 snRNA and analyze the kinetics of U6 nucleolar localization after injection of in vitro transcribed fluorescein-labeled transcripts into Xenopus laevis oocytes. In contrast to U3 small nucleolar RNA (snoRNA) which developed strong nucleolar labeling over 4 h and maintained strong nucleolar signals through 24 h, U6 snRNA localized to nucleoli immediately after injection, but nucleolar staining decreased after 4 h. By 24 h after injection of U6 snRNA, only weak nucleolar signals were observed. Unlike the time-dependent profile of strong nucleolar localization of U6 snRNA or U3 snoRNA, injection of fluorescein-labeled U2 snRNA gave weak nucleolar staining at all times throughout a 24-h period; U2 snRNA modifications are believed to occur outside of the nucleolus. The notion that the decrease of U6 signals over time was due to its trafficking out of nucleoli and not to transcript degradation was supported by the demonstration of U6 snRNA stability over time. Therefore, in contrast to snoRNAs like U3, U6 snRNA transiently passes through nucleoli.

scholarly journals Synthetic Lethality of Yeast slt Mutations with U2 Small Nuclear RNA Mutations Suggests Functional Interactions between U2 and U5 snRNPs That Are Important for Both Steps of Pre-mRNA Splicing

1998 ◽  
Vol 18 (4) ◽  
pp. 2055-2066 ◽  
Author(s):  
Deming Xu ◽  
Deborah J. Field ◽  
Shou-Jiang Tang ◽  
Arnaud Moris ◽  
Brian P. Bobechko ◽  
...  
Keyword(s):  
Synthetic Lethality ◽  
Mrna Splicing ◽  
Splicing Factors ◽  
Small Nuclear Rna ◽  
U2 Snrna ◽  
U6 Snrna ◽  
Two Factors ◽  
Synthetically Lethal ◽  
U5 Snrna ◽  
New Alleles

ABSTRACT A genetic screen was devised to identify Saccharomyces cerevisiae splicing factors that are important for the function of the 5′ end of U2 snRNA. Six slt (stands for synthetic lethality with U2) mutants were isolated on the basis of synthetic lethality with a U2 snRNA mutation that perturbs the U2-U6 snRNA helix II interaction. SLT11 encodes a new splicing factor andSLT22 encodes a new RNA-dependent ATPase RNA helicase (D. Xu, S. Nouraini, D. Field, S. J. Tang, and J. D. Friesen, Nature 381:709–713, 1996). The remaining four sltmutations are new alleles of previously identified splicing genes:slt15, previously identified as prp17(slt15/prp17-100), slt16/smd3-1,slt17/slu7-100, and slt21/prp8-21. slt11-1 andslt22-1 are synthetically lethal with mutations in the 3′ end of U6 snRNA, a region that affects U2-U6 snRNA helix II; however,slt17/slu7-100 and slt21/prp8-21 are not. This difference suggests that the latter two factors are unlikely to be involved in interactions with U2-U6 snRNA helix II but rather are specific to interactions with U2 snRNA. Pairwise synthetic lethality was observed among slt11-1 (which affects the first step of splicing) and several second-step factors, includingslt15/prp17-100, slt17/slu7-100, andprp16-1. Mutations in loop 1 of U5 snRNA, a region that is implicated in the alignment of the two exons, are synthetically lethal with slu4/prp17-2 and slu7-1 (D. Frank, B. Patterson, and C. Guthrie, Mol. Cell. Biol. 12:5179–5205, 1992), as well as with slt11-1, slt15/prp17-100,slt17/slu7-100, and slt21/prp8-21. These same U5 snRNA mutations also interact genetically with certain U2 snRNA mutations that lie in the helix I and helix II regions of the U2-U6 snRNA structure. Our results suggest interactions among U2 snRNA, U5 snRNA, and Slt protein factors that may be responsible for coupling and coordination of the two reactions of pre-mRNA splicing.

scholarly journals METTL16, Methyltransferase-Like Protein 16: Current Insights into Structure and Function

2021 ◽  
Vol 22 (4) ◽  
pp. 2176
Author(s):  
Agnieszka Ruszkowska
Keyword(s):  
Current Knowledge ◽  
Molecular Structures ◽  
Structural Basis ◽  
Small Nuclear Rna ◽  
Functional Studies ◽  
U6 Snrna ◽  
Non Coding Rna ◽  
Sam Synthetase ◽  
Lncrna Malat1 ◽  
And Function

Methyltransferase-like protein 16 (METTL16) is a human RNA methyltransferase that installs m6A marks on U6 small nuclear RNA (U6 snRNA) and S-adenosylmethionine (SAM) synthetase pre-mRNA. METTL16 also controls a significant portion of m6A epitranscriptome by regulating SAM homeostasis. Multiple molecular structures of the N-terminal methyltransferase domain of METTL16, including apo forms and complexes with S-adenosylhomocysteine (SAH) or RNA, provided the structural basis of METTL16 interaction with the coenzyme and substrates, as well as indicated autoinhibitory mechanism of the enzyme activity regulation. Very recent structural and functional studies of vertebrate-conserved regions (VCRs) indicated their crucial role in the interaction with U6 snRNA. METTL16 remains an object of intense studies, as it has been associated with numerous RNA classes, including mRNA, non-coding RNA, long non-coding RNA (lncRNA), and rRNA. Moreover, the interaction between METTL16 and oncogenic lncRNA MALAT1 indicates the existence of METTL16 features specifically recognizing RNA triple helices. Overall, the number of known human m6A methyltransferases has grown from one to five during the last five years. METTL16, CAPAM, and two rRNA methyltransferases, METTL5/TRMT112 and ZCCHC4, have joined the well-known METTL3/METTL14. This work summarizes current knowledge about METTL16 in the landscape of human m6A RNA methyltransferases.

The BAF chromatin remodeling complexes: structure, function, and synthetic lethalities

2021 ◽  
Author(s):  
Julia Varga ◽  
Marie Kube ◽  
Katja Luck ◽  
Sandra Schick
Keyword(s):  
Large Scale ◽  
Treatment Modalities ◽  
Chromatin Remodelers ◽  
Baf Complex ◽  
Synthetic Lethal ◽  
Physiological Processes ◽  
Molecular Action ◽  
Synthetic Lethal Interactions ◽  
Chromatin Remodeling Complexes ◽  
And Function

BAF complexes are multi-subunit chromatin remodelers, which have a fundamental role in genomic regulation. Large-scale sequencing efforts have revealed frequent BAF complex mutations in many human diseases, particularly in cancer and neurological disorders. These findings not only underscore the importance of the BAF chromatin remodelers in cellular physiological processes, but urge a more detailed understanding of their structure and molecular action to enable the development of targeted therapeutic approaches for diseases with BAF complex alterations. Here, we review recent progress in understanding the composition, assembly, structure, and function of BAF complexes, and the consequences of their disease-associated mutations. Furthermore, we highlight intra-complex subunit dependencies and synthetic lethal interactions, which have emerged as promising treatment modalities for BAF-related diseases.

Synthetic Lethal Interactions in Cancer Therapy

2017 ◽  
Vol 17 (4) ◽  
pp. 304-310 ◽  
Author(s):  
Xinwei Geng ◽  
Xiaohui Wang ◽  
Dan Zhu ◽  
Songmin Ying
Keyword(s):  
Cancer Therapy ◽  
Synthetic Lethal ◽  
Synthetic Lethal Interactions

Establishing a model to demonstrate physical and mathematical properties of chromatin fibres in fission yeast cells - Research in the Molecular Biophysics Lab at Hiroshima University

Impact ◽  
2018 ◽  
Vol 2018 (3) ◽  
pp. 89-91
Author(s):  
Shin-ichi Tate
Keyword(s):  
Molecular Biology ◽  
Yeast Cells ◽  
Molecular Architecture ◽  
Ministry Of Education ◽  
Cellular Functions ◽  
Sports Science ◽  
Cellular Events ◽  
And Function ◽  
Education Culture ◽  
Open The Doors

The field of molecular biology has provided great insights into the structure and function of key molecules. Thanks to this area of research, we can now grasp the biological details of DNA and have characterised an enormous number of molecules in massive data bases. These 'biological periodic tables' have allowed scientists to connect molecules to particular cellular events, furthering scientific understanding of biological processes. However, molecular biology has yet to answer questions regarding 'higher-order' molecular architecture, such as that of chromatin. Chromatin is the molecular material that serves as the building block for chromosomes, the structures that carry an organism's genetic information inside of the cell's nucleus. Understanding the physical properties of chromatin is crucial in developing a more thorough picture of how chromatin's structure relate to its key cellular functions. Moreover, by establishing a physical model of chromatin, scientists will be able to open the doors into the true inner workings of the cell nucleus. Professor Shin-ichi Tate and his team of researchers at Hiroshima University's Research Center for the Mathematics on Chromatin Live Dynamics (RcMcD), are attempting to do just that. Through a five-year grant funded by the Platform for Dynamic Approaches to Living Systems from the Ministry of Education, Culture, Sports, Science and Technology, Tate is aiming to gain a clearer understanding of the structure and dynamics of chromatin.

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