scholarly journals Structural and Functional Insights into Human Nuclear Cyclophilins

2018 ◽  
Author(s):  
Carol Rajiv ◽  
Tara L. Davis
Keyword(s):  
Chromatin Modification ◽  
Human Cells ◽  
Mrna Splicing ◽  
Current Work ◽  
Cellular Biology ◽  
Future Directions ◽  
Peptidyl Prolyl Isomerases ◽  
Specific Inhibitors

The peptidyl-prolyl isomerases of the cyclophilin type are distributed throughout human cells, including eight found solely in the nucleus. Nuclear cyclophilins are involved in complexes that regulate chromatin modification, transcription, and pre-mRNA splicing. This review collects what is known about the eight human nuclear cyclophilins: PPIH, PPIE, PPIL1, PPIL2, PPIL3, PPIG, CWC27, and PPWD1. Each “spliceophilin” is evaluated in relation to the spliceosomal complex in which it has been studied, and current work studying the biological roles of these cyclophilins in the nucleus are discussed. All eight of the human splicing complexes available in the PDB are analyzed from the viewpoint of the human spliceophilins. Future directions in structural and cellular biology, and the importance of developing spliceophilin-specific inhibitors, are considered.

scholarly journals Structural and Functional Insights into Human Nuclear Cyclophilins

Biomolecules ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 161 ◽  
Author(s):  
Caroline Rajiv ◽  
Tara Davis
Keyword(s):  
Protein Data Bank ◽  
Chromatin Modification ◽  
Data Bank ◽  
Mrna Splicing ◽  
Cellular Biology ◽  
Prolyl Isomerase ◽  
Future Directions ◽  
Peptidyl Prolyl Isomerase ◽  
Peptidyl Prolyl Isomerases ◽  
Specific Inhibitors

The peptidyl prolyl isomerases (PPI) of the cyclophilin type are distributed throughout human cells, including eight found solely in the nucleus. Nuclear cyclophilins are involved in complexes that regulate chromatin modification, transcription, and pre-mRNA splicing. This review collects what is known about the eight human nuclear cyclophilins: peptidyl prolyl isomerase H (PPIH), peptidyl prolyl isomerase E (PPIE), peptidyl prolyl isomerase-like 1 (PPIL1), peptidyl prolyl isomerase-like 2 (PPIL2), peptidyl prolyl isomerase-like 3 (PPIL3), peptidyl prolyl isomerase G (PPIG), spliceosome-associated protein CWC27 homolog (CWC27), and peptidyl prolyl isomerase domain and WD repeat-containing protein 1 (PPWD1). Each “spliceophilin” is evaluated in relation to the spliceosomal complex in which it has been studied, and current work studying the biological roles of these cyclophilins in the nucleus are discussed. The eight human splicing complexes available in the Protein Data Bank (PDB) are analyzed from the viewpoint of the human spliceophilins. Future directions in structural and cellular biology, and the importance of developing spliceophilin-specific inhibitors, are considered.

The phylogenetically invariant ACAGAGA and AGC sequences of U6 small nuclear RNA are more tolerant of mutation in human cells than in Saccharomyces cerevisiae

1993 ◽  
Vol 13 (9) ◽  
pp. 5377-5382
Author(s):  
B Datta ◽  
A M Weiner
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Transient Expression ◽  
Human Cells ◽  
Mrna Splicing ◽  
Small Nuclear Rna ◽  
Transient Expression Assay ◽  
U6 Snrna ◽  
Nuclear Rna

U6 small nuclear RNA (snRNA) is the most highly conserved of the five spliceosomal snRNAs that participate in nuclear mRNA splicing. The proposal that U6 snRNA plays a key catalytic role in splicing [D. Brow and C. Guthrie, Nature (London) 337:14-15, 1989] is supported by the phylogenetic conservation of U6, the sensitivity of U6 to mutation, cross-linking of U6 to the vicinity of the 5' splice site, and genetic evidence for extensive base pairing between U2 and U6 snRNAs. We chose to mutate the phylogenetically invariant 41-ACAGAGA-47 and 53-AGC-55 sequences of human U6 because certain point mutations within the homologous regions of Saccharomyces cerevisiae U6 selectively block the first or second step of mRNA splicing. We found that both sequences are more tolerant to mutation in human cells (assayed by transient expression in vivo) than in S. cerevisiae (assayed by effects on growth or in vitro splicing). These differences may reflect different rate-limiting steps in the particular assays used or differential reliance on redundant RNA-RNA or RNA-protein interactions. The ability of mutations in U6 nucleotides A-45 and A-53 to selectively block step 2 of splicing in S. cerevisiae had previously been construed as evidence that these residues might participate directly in the second chemical step of splicing; an indirect, structural role seems more likely because the equivalent mutations have no obvious phenotype in the human transient expression assay.

scholarly journals The Development of a Conceptual Framework and Tools to Assess Undergraduates' Principled Use of Models in Cellular Biology

2010 ◽  
Vol 9 (4) ◽  
pp. 441-452 ◽  
Author(s):  
Gail Richmond ◽  
Brett Merritt ◽  
Mark Urban-Lurain ◽  
Joyce Parker
Keyword(s):  
Education Reform ◽  
Conceptual Understanding ◽  
Assessment Tool ◽  
Critical Role ◽  
Cellular Biology ◽  
Science Education Reform ◽  
Assessment Framework ◽  
Future Directions ◽  
Large Enrollment ◽  
Use Of Models

Recent science education reform has been marked by a shift away from a focus on facts toward deep, rich, conceptual understanding. This requires assessment that also focuses on conceptual understanding rather than recall of facts. This study outlines our development of a new assessment framework and tool—a taxonomy— which, unlike existing frameworks and tools, is grounded firmly in a framework that considers the critical role that models play in science. It also provides instructors a resource for assessing students' ability to reason about models that are central to the organization of key scientific concepts. We describe preliminary data arising from the application of our tool to exam questions used by instructors of a large-enrollment cell and molecular biology course over a 5-yr period during which time our framework and the assessment tool were increasingly used. Students were increasingly able to describe and manipulate models of the processes and systems being studied in this course as measured by assessment items. However, their ability to apply these models in new contexts did not improve. Finally, we discuss the implications of our results and the future directions for our research.

Biblical Border Slippage and Feminist Postcolonial Criticism

2020 ◽  
pp. 229-246
Author(s):  
Judith E. McKinlay
Keyword(s):  
Critical Theory ◽  
Postcolonial Studies ◽  
Current Work ◽  
Future Directions ◽  
Postcolonial Criticism ◽  
Ethical Choices ◽  
Biblical Texts ◽  
Good And Evil ◽  
Biblical Figures ◽  
Selection Of

The essay takes as its cue the biblical figures of Eve and Wisdom, both of whom slip through the divine/human border. Eve brings knowledge of good and evil and Wisdom offers a concern for human ethical choices. For what characterizes feminist and postcolonial studies is the hope and ideal of a future of respect for all. A discussion of feminist postcolonial critical theory and current work in the field assesses that despite differing methodologies scholars share a concern for the ways in which women are represented and frequently “othered” in border-slipping texts. The study also considers a selection of biblical texts from a range of eras and political circumstances to illustrate these varying representations. The essay concludes with a reflection on the significance of the work and attempts to predict future directions.

The Social Experience of Entertainment Media

2011 ◽  
Vol 23 (3) ◽  
pp. 111-121 ◽  
Author(s):  
Randi Shedlosky-Shoemaker ◽  
Kristi A. Costabile ◽  
Haylee K. DeLuca ◽  
Robert M. Arkin
Keyword(s):  
Social Media ◽  
Social Influence ◽  
Social Experience ◽  
Current Work ◽  
Entertainment Media ◽  
Future Directions ◽  
Peer Evaluations ◽  
The Social

People often look to others for guidance when selecting narrative entertainment. Previous work has demonstrated that this social guidance forms the basis of people’s expectations and subsequently affects people’s experience. The current work extends previous research by exploring the influence of peer evaluations of a story, on enjoyment of and psychological transportation in the written narrative. In two experiments, participants read peer evaluations prior to reading the story. Results of Experiment 1 revealed that social influence guides readers’ expectations, attention to elements in the narrative, reported enjoyment, and feelings of transportation in the narrative. This influence was particularly apparent when readers were given unfavorable reviews of the stimulus. In the second experiment, readers were given peer evaluations that were either confirmed or disconfirmed by other readers. Results indicated that valence of peer evaluations influenced both transportation and enjoyment. Additionally, inconsistent evaluations increased feelings of transportation, but consistency alone had no effect on reported enjoyment. Implications for social media experiences and future directions in research on entertainment media are discussed.

scholarly journals METTL4 catalyzes m6Am methylation in U2 snRNA to regulate pre-mRNA splicing

2020 ◽  
Vol 48 (16) ◽  
pp. 9250-9261
Author(s):  
Yeek Teck Goh ◽  
Casslynn W Q Koh ◽  
Donald Yuhui Sim ◽  
Xavier Roca ◽  
W S Sho Goh
Keyword(s):  
Rna Processing ◽  
Human Cells ◽  
Mrna Splicing ◽  
U2 Snrna ◽  
Mrna Transcripts ◽  
Single Base Resolution ◽  
Accelerated Studies ◽  
Rna Motif ◽  
Target Rna

Abstract N 6-methylation of 2′-O-methyladenosine (Am) in RNA occurs in eukaryotic cells to generate N6,2′-O-dimethyladenosine (m6Am). Identification of the methyltransferase responsible for m6Am catalysis has accelerated studies on the function of m6Am in RNA processing. While m6Am is generally found in the first transcribed nucleotide of mRNAs, the modification is also found internally within U2 snRNA. However, the writer required for catalyzing internal m6Am formation had remained elusive. By sequencing transcriptome-wide RNA methylation at single-base-resolution, we identified human METTL4 as the writer that directly methylates Am at U2 snRNA position 30 into m6Am. We found that METTL4 localizes to the nucleus and its conserved methyltransferase catalytic site is required for U2 snRNA methylation. By sequencing human cells with overexpressed Mettl4, we determined METTL4’s in vivo target RNA motif specificity. In the absence of Mettl4 in human cells, U2 snRNA lacks m6Am thereby affecting a subset of splicing events that exhibit specific features such as 3′ splice-site weakness and an increase in exon inclusion. These findings suggest that METTL4 methylation of U2 snRNA regulates splicing of specific pre-mRNA transcripts.

scholarly journals UBL5 is essential for pre‐ mRNA splicing and sister chromatid cohesion in human cells

EMBO Reports ◽  
2014 ◽  
Vol 15 (9) ◽  
pp. 956-964 ◽  
Author(s):  
Yasuyoshi Oka ◽  
Hanne Varmark ◽  
Kristoffer Vitting‐Seerup ◽  
Petra Beli ◽  
Johannes Waage ◽  
...  
Keyword(s):  
Sister Chromatid ◽  
Sister Chromatid Cohesion ◽  
Human Cells ◽  
Mrna Splicing ◽  
Chromatid Cohesion
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