Structural and Biochemical Studies of the Human Pre-mRNA 3'-end Processing Complex PDF Download
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Author: Keith Hamilton
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Most eukaryotic pre-mRNAs undergo 3′-end cleavage and polyadenylation prior to their export from the nucleus. A large number of proteins in several complexes participate in this 3′-end processing, including cleavage and polyadenylation specificity factor (CPSF) in mammals. The CPSF can be further divided into two sub-complexes: mPSF (mammalian polyadenylation specificity factor) which recognizes the AAUAAA polyadenylation signal (PAS) in the pre- mRNA, and mCF (mammalian cleavage factor) which cleaves the RNA. mPSF consists of CPSF160, CPSF30, WDR33, and hFip1. This thesis shows that AAUAAA PAS is recognized with ∼3 nM affinity by the CPSF160-WDR33-CPSF30 ternary complex, while the proteins alone or the binary complexes do not bind the PAS with high affinity. Furthermore, it is shown that mutations of residues in CPSF30 that have van der Waals interactions with the bases of the PAS lead to a sharp reduction in the affinity. Finally, variations of the AAUAAA or removing the bases downstream also reduce the binding significantly.
Author: Keith Hamilton
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Most eukaryotic pre-mRNAs undergo 3′-end cleavage and polyadenylation prior to their export from the nucleus. A large number of proteins in several complexes participate in this 3′-end processing, including cleavage and polyadenylation specificity factor (CPSF) in mammals. The CPSF can be further divided into two sub-complexes: mPSF (mammalian polyadenylation specificity factor) which recognizes the AAUAAA polyadenylation signal (PAS) in the pre- mRNA, and mCF (mammalian cleavage factor) which cleaves the RNA. mPSF consists of CPSF160, CPSF30, WDR33, and hFip1. This thesis shows that AAUAAA PAS is recognized with ∼3 nM affinity by the CPSF160-WDR33-CPSF30 ternary complex, while the proteins alone or the binary complexes do not bind the PAS with high affinity. Furthermore, it is shown that mutations of residues in CPSF30 that have van der Waals interactions with the bases of the PAS lead to a sharp reduction in the affinity. Finally, variations of the AAUAAA or removing the bases downstream also reduce the binding significantly.
Author: Angus I. Lamond
Publisher: Springer Science & Business Media
ISBN: 3662223252
Category : Science
Languages : en
Pages : 230
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Book Description
he past fifteen years have seen tremendous growth in our understanding of T the many post-transcriptional processing steps involved in producing func tional eukaryotic mRNA from primary gene transcripts (pre-mRNA). New processing reactions, such as splicing and RNA editing, have been discovered and detailed biochemical and genetic studies continue to yield important new insights into the reaction mechanisms and molecular interactions involved. It is now apparent that regulation of RNA processing plays a significant role in the control of gene expression and development. An increased understanding of RNA processing mechanisms has also proved to be of considerable clinical importance in the pathology of inherited disease and viral infection. This volume seeks to review the rapid progress being made in the study of how mRNA precursors are processed into mRNA and to convey the broad scope of the RNA field and its relevance to other areas of cell biology and medicine. Since one of the major themes of RNA processing is the recognition of specific RNA sequences and structures by protein factors, we begin with reviews of RNA-protein interactions. In chapter 1 David Lilley presents an overview of RNA structure and illustrates how the structural features of RNA molecules are exploited for specific recognition by protein, while in chapter 2 Maurice Swanson discusses the structure and function of the large family of hnRNP proteins that bind to pre-mRNA. The next four chapters focus on pre-mRNA splicing.
Author:
Publisher: Academic Press
ISBN: 0128235748
Category : Science
Languages : en
Pages : 502
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Book Description
mRNA 3’ End Processing and Stability, Volume 655 in the Methods in Enzymology series, highlights new advances in the field, with this new volume presenting interesting chapters on a variety of timely topics. Each chapter is written by an international board of authors. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Methods in Enzymology series Updated release includes the latest information on mRNA 3' End Processing and Stability
Author: Yixuan Wu
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
The Integrator complex (INT) is a metazoan-specific group of proteins associated with RNA polymerase II (Pol II) that has important functions in the 3'-end processing of noncodng RNAs, including uridine-rich small nuclear RNA (UsnRNA) and enhancer RNA (eRNA). Recently, INT has also been reported to be involved in Pol II transcriptional regulation of protein-encoding genes. INT contains at least 14 subunits, but the function of each subunit is difficult to predicted, because most subunits lack identifiable domains and display little similarity with other proteins. The endonuclease activity of INT is carried out by its subunit 11 (IntS11), which belongs to the metallo--lactamase superfamily and is a paralog of CPSF-73, the endonuclease for pre-mRNA 3'-end processing. IntS11 forms a stable complex with INT subunit 9 (IntS9) through their C-terminal domains (CTDs). This dissertation describes the crystal structure of the IntS9-IntS11 CTD complex at 2.1-Å resolution and summaries the structure-based biochemical and functional studies.
Author: Angus I. Lamond
Publisher: Springer
ISBN: 9783662223277
Category : Science
Languages : en
Pages : 221
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Book Description
he past fifteen years have seen tremendous growth in our understanding of T the many post-transcriptional processing steps involved in producing func tional eukaryotic mRNA from primary gene transcripts (pre-mRNA). New processing reactions, such as splicing and RNA editing, have been discovered and detailed biochemical and genetic studies continue to yield important new insights into the reaction mechanisms and molecular interactions involved. It is now apparent that regulation of RNA processing plays a significant role in the control of gene expression and development. An increased understanding of RNA processing mechanisms has also proved to be of considerable clinical importance in the pathology of inherited disease and viral infection. This volume seeks to review the rapid progress being made in the study of how mRNA precursors are processed into mRNA and to convey the broad scope of the RNA field and its relevance to other areas of cell biology and medicine. Since one of the major themes of RNA processing is the recognition of specific RNA sequences and structures by protein factors, we begin with reviews of RNA-protein interactions. In chapter 1 David Lilley presents an overview of RNA structure and illustrates how the structural features of RNA molecules are exploited for specific recognition by protein, while in chapter 2 Maurice Swanson discusses the structure and function of the large family of hnRNP proteins that bind to pre-mRNA. The next four chapters focus on pre-mRNA splicing.
Author: Ingela Wetterberg
Publisher:
ISBN: 9789173490177
Category :
Languages : en
Pages : 61
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Book Description
Author:
Publisher:
ISBN: 9780815332183
Category : Cells
Languages : en
Pages : 0
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Author:
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Another protein, Rtr1, was recently suggested to function as a pSer5 phosphatase in a zinc-dependent fashion, separately or redundantly with Ssu72. We solved the crystal structure of Rtr1 and discovered a new type of zinc finger with no close structural homologs. Unexpectedly, Rtr1 does not present any evidence of an active site and it lacks detectable phosphatase activity in all our assays. We believe that, based on our results, Rtr1 does not have catalytic ability but instead indirectly regulate the phosphorylation state of the CTD. In summary, our studies on the symplein-Ssu72-CTD complex as well as Rtr1 have revealed several novel structural features that are essential for the CTD regulation at the atomic level. These results will also shed light on understanding the mechanism by which RNAP II transcription and RNA processing are coupled.
Author: Qin Yang
Publisher:
ISBN:
Category :
Languages : en
Pages : 338
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Book Description
These crystal structures not only elucidated the molecular mechanism for sequence specific recognition, but also led to an exciting model for how CFlm may regulate alternative poly(A) site usage. In parallel, we have successfully obtained crystals of a disulfide cross-linked PAP-RNA complex, by implementing a method previously applied to protein-DNA complexes. A structure of a PAP-RNA complex might elucidate the mechanism PAP employs to specifically recognize ATP and uncover the path the RNA follows when bound by the polymerase.
Author: Torben Heick Jensen
Publisher: Springer Science & Business Media
ISBN: 1441978410
Category : Medical
Languages : en
Pages : 161
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Book Description
The diversity of RNAs inside living cells is amazing. We have known of the more “classic” RNA species: mRNA, tRNA, rRNA, snRNA and snoRNA for some time now, but in a steady stream new types of molecules are being described as it is becoming clear that most of the genomic information of cells ends up in RNA. To deal with the enormous load of resulting RNA processing and degradation reactions, cells need adequate and efficient molecular machines. The RNA exosome is arising as a major facilitator to this effect. Structural and functional data gathered over the last decade have illustrated the biochemical importance of this multimeric complex and its many co-factors, revealing its enormous regulatory power. By gathering some of the most prominent researchers in the exosome field, it is the aim of this volume to introduce this fascinating protein complex as well as to give a timely and rich account of its many functions. The exosome was discovered more than a decade ago by Phil Mitchell and David Tollervey by its ability to trim the 3’end of yeast, S. cerevisiae, 5. 8S rRNA. In a historic account they laid out the events surrounding this identification and the subsequent birth of the research field. In the chapter by Kurt Januszyk and Christopher Lima the structural organization of eukaryotic exosomes and their evolutionary counterparts in bacteria and archaea are discussed in large part through presentation of structures.
