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Topic: Spliceosome

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	Spliceosome disassembly catalyzed by Prp43 and its associated components Ntr1 and Ntr2 -- Tsai et al. 19 (24): 2991 -- ...
		Splicing assays, immunoprecipitation, immunodepletion, and precipitation of the spliceosome by streptavidin agarose
		Precipitation of the spliceosome with streptavidin agarose was
		Burge, C.B., Tuschl, T.H., and Sharp, P.A. Splicing of precursors to mRNAs by the spliceosome.
	www.genesdev.org /cgi/content/full/19/24/2991 (6852 words)

	Definition of a spliceosome interaction domain in yeast Prp2 ATPase -- EDWALDS-GILBERT et al. 10 (2): 210 -- RNA
		to the spliceosome and are inactive for splicing.
		bind tightly to the spliceosome in the absence of ATP (Fig.
		with the spliceosome, and (2) the N terminus of Prp2 is dispensable
	www.rnajournal.org /cgi/content/full/10/2/210 (5449 words)

	UC Santa Cruz - Press Release
		The spliceosome is the key to understanding how the body's cells control the process of alternative splicing to ensure that the right protein gets made at the right place and time.
		Jurica is using several techniques to study the structure of the spliceosome, including electron microscopy and x-ray crystallography.
		She is also using biochemical techniques to investigate how the spliceosome is assembled from smaller components and how it carries out its functions.
	www.ucsc.edu /news_events/press_releases/text.asp?pid=667 (697 words)

	UCSF Magazine: Christine Guthrie: Tales from the Spliceosome
		The spliceosome has to be one of the strangest words - and wondrous wizards - of evolution.
		All this was far from Guthrie's mind when she took up the challenge that yeast spliceosomes even existed, much less that they were a worthy model.
		That is, in another symbol of evolution's versatility, the spliceosome sometimes skips over part of the coding region of a gene, thereby altering the blueprint of the subsequent protein.
	pub.ucsf.edu /magazine/200305/guthrie.html (770 words)

	Spliceosome - Wikipedia, the free encyclopedia
		A spliceosome is a complex of RNA and many protein subunits called snRNP's, that removes the non-coding introns from unprocessed mRNA.
		Spliceosomes are unique to eukaryotic mRNA as the mRNA of prokaryotes lack introns.
		In accordance with the GU-AG rule, all introns have a 5' GU and a 3' AG recognition sequence which the spliceosome recognizes and excises as a lariat whereby the sequence is subsequently destroyed.
	en.wikipedia.org /wiki/Spliceosome (361 words)

	UCSC Biomedical Research - Prof. Melissa Jurica
		The spliceosome is a large cellular machine that is critical to the process of gene expression.
		Jurica and her laboratory are using the tools of structural biology to characterize the architecture of the entire spliceosome, as well as to provide detailed information concerning its approximately 200 components.
		With the spliceosome, the task is even more formidable due to its dynamic assembly, lack of symmetry and possible structural flexibility.
	biomedical.ucsc.edu /Jurica.html (503 words)

	The Guthrie Lab: Publications (Site not responding. Last check: 2007-11-05)
		Wang, Y. and Guthrie, C. (1998) Prp16, a DEAH-box RNA helicase, is recruited onto the spliceosome primarily via its non-conserved N-terminal domain.
		Madhani, H. and Guthrie, C. (1994) Genetic interactions betwen the RNA helicase homolog Prp16 and spliceosomal snRNAs identify candidate ligands for the Prp16 RNA-dependent ATPase.
		Schwer, B. and Guthrie, C. (1992) A conformational rearrangement in the spliceosome is dependent on PRP16 and ATP hydrolysis.
	www.ucsf.edu /guthrie/publications.htm (1788 words)

	Laboratory of Ren-Jang Lin, PhD
		The spliceosome is composed of five small nuclear RNAs and about a hundred of proteins, whose function is to recognize and splice exons together.
		Since the spliceosome is a metalloenzyme, finding the spliceosomal components that coordinate catalytic metals is crucial in addressing the question.
		Thus, these observations support the idea that U6 snRNA is not only at the core of the spliceosome but also directly participates in the chemical reaction of splicing, and that the spliceosome may have a evolutionary root in RNA-based machinery.
	www.cityofhope.org /LinLab/res_project1.asp (178 words)

	Kiyoshi Nagai: Crystallographic and Biochemical studies of the spliceosome
		The molecular mass of the spliceosome is estimated to be over 6 MDa based on the proteomic analysis of its protein components.
		Considering its sheer size, its dynamic nature and the amount present in natural cells it is not feasible to crystallise the whole spliceosome.
		The structure of these sub-assemblies will be fitted into the cryo-EM structure of the spliceosome trapped at different steps along the splicing cycle to gain insight into its overall architecture.
	www2.mrc-lmb.cam.ac.uk /projects/nagai.html (429 words)

	YOUNG SCIENTIST AWARD: Construction of a Minimal, Protein-Free Spliceosome -- Valadkhan 307 (5711): 863 -- Science
		Consistent with its critical role, the spliceosome (the massive ribonucleoprotein particle that catalyzes splicing) has been shown to be the largest and most complicated molecular machine known (1).
		The complexity of the spliceosome stems not only from its large number of components--almost 300 proteins and five small nuclear RNAs (snRNAs)--but also from the fact that the spliceosome is dynamic, assembling for each splicing event in an elaborate and stepwise fashion involving multiple rearrangements and conformational changes.
		In addition to providing direct evidence for RNA catalysis in the spliceosome and thus settling the longstanding and central question of identity of the catalytic domain, the minimal system provides a powerful tool for studying the spliceosome.
	www.sciencemag.org /cgi/content/full/307/5711/863 (1303 words)

	MCDB Faculty - Melissa Jurica
		Our current focus is the spliceosome, a large protein/RNA complex responsible for editing the information contained in the RNA transcripts of over 90% of human genes.
		The spliceosome is dynamically assembled on every intron from 5 structural RNAs and on the order of 100 different proteins.
		As we solve more structures of the spliceosome and its components we will be able to combine our biochemical studies to create highly detailed 3D models of the spliceosome.
	www.biology.ucsc.edu /faculty/jurica.html (407 words)

	[No title]
		In particular we are interested in pre-mRNA splicing, in which the noncoding intron sequences are removed from the pre-mRNA molecules by the spliceosome.
		The aim of our research is to understand the significance and function of the U12-dependent spliceosome in vertebrates using both genetic and biochemical analyses.
		In this approach we are investigating regulation of the U12-dependent spliceosome in vivo by manipulating the activity of the spliceosome in either cell lines or in whole organisms.
	www.biocenter.helsinki.fi /bi/SPLICING/index.html (234 words)

	The Prp19p-Associated Complex in Spliceosome Activation -- Chan et al. 302 (5643): 279 -- Science
		Spliceosome disassembly catalyzed by Prp43 and its associated components Ntr1 and Ntr2.
		SNEV is an evolutionarily conserved splicing factor whose oligomerization is necessary for spliceosome assembly.
		New tertiary constraints between the RNA components of active yeast spliceosomes: A photo-crosslinking study.
	www.sciencemag.org /cgi/content/abstract/302/5643/279 (693 words)

	geg research
		In Dr. Ren-Jang Lin’s lab at the City of Hope I studied an extrinsic splicing factor called Prp2, which is a protein required prior to the first transesterification reaction in pre-messenger RNA splicing.
		Previous work in Dr. Lin’s lab demonstrated that the Prp2 protein binds to the spliceosome in the absence of ATP and is released from the spliceosome following ATP hydrolysis, and in doing so activates the spliceosome for the first catalytic step of splicing.
		We have analyzed the functions of different domains of the Prp2 protein to determine what regions are required for spliceosome binding and release as well as ATP hydrolysis activity.
	faculty.jsd.claremont.edu /gedwalds/gegres.htm (946 words)

	ATP-Dependent Remodeling of the Spliceosome: Intragenic Suppressors of Release-Defective Mutants of Saccharomyces ...
		ATP-Dependent Remodeling of the Spliceosome: Intragenic Suppressors of Release-Defective Mutants of Saccharomyces cerevisiae Prp22 -- Campodonico and Schwer 160 (2): 407 -- Genetics
		release of mRNA from the spliceosome in vitro (
		The inability of T637A to catalyze spliceosome disassembly
	www.genetics.org /cgi/content/full/160/2/407 (4508 words)

	NEW STUDY GIVES SCIENTISTS INSIGHT INTO HOW THE DNA CODE IS TURNED INTO INSTRUCTIONS FOR PROTEIN CONSTRUCTION (Site not responding. Last check: 2007-11-05)
		Since the discovery, around 25 years ago, that the bits of DNA in the genes that code for protein formation are interspersed with "filler" segments that have no known function, scientists have worked to understand the process by which the right sequences are lifted out and strung together to make a coherent set of instructions.
		Their task was made difficult by the fact that spliceosomes in living cells are made up of four identical modules strung together like beads on a strand of RNA, each a miniature spliceosome capable of splicing on its own.
		Whereas researchers examining splicing in test tubes saw evidence of a complicated sequence of events in which the spliceosome machinery assembles itself anew for each splicing job, the team's investigations of spliceosomes from live cells found splicing to take place in pre-formed machines.
	www.newmaterials.com /news/5797.asp (682 words)

	Genome Biology \| Full text \| Challenging the spliceosome machine
		This observation suggests that the spliceosome machinery is strained by both longer and shorter exons, and is least strained for exons of intermediate length.
		Previous studies have provided evidence suggesting that the spliceosome brings together pairs of exon or intron ends, a process referred to as exon and intron definition [19,24].
		Recent mass spectrometry and associated studies [25-29] suggest that the spliceosome is a complex macromolecular machine that is pre-assembled prior to binding of pre-mRNA, consistent with the model that it might present an ordered interaction surface for binding of groups of splice sites.
	genomebiology.com /2006/7/1/R3 (6483 words)

	SUB Göttingen - Dissertationen - Böhringer, Daniel : Elektronenmikroskopische 3D Strukturbestimmung des ...
		In order to elucidate the conformational changes of the spliceosome that occur during its catalytic activation it is necessary to obtain high resolution 3D structures.
		The 3D structure of the spliceosome helps to understand how eukaryotic gene expression is regulated at the RNA level.
		On the other hand, the flexibility of the head domain could be of functional importance for the integration of the Prp19 protein complex, that is essential for catalytic activation.
	webdoc.sub.gwdg.de /diss/2005/boehringer (710 words)

	Distinct domains of splicing factor Prp8 mediate different aspects of spliceosome activation -- Kuhn et al. 99 (14): ...
		Prp8 is the largest and most highly conserved protein in the spliceosome yet its mechanism of function is poorly understood.
		Shown is a schematic of the RNA rearrangements that are proposed to be inhibited by the U4-cs1 mutation (position indicated by "xxx") and stimulated by the U6-UA mutation (positions indicated by asterisks).
		Prp8 is proposed to coordinate the rearrangements catalyzed by Prp28 and Prp44/Brr2 by repressing the activities of these factors until the spliceosome is completely assembled and properly aligned on an authentic intron.
	www.pnas.org /cgi/content/full/99/14/9145 (3381 words)

	sjbr/1998/Brajenovic
		The formation of a spliceosome complex takes place in the RNA editing proces, where a newly synthesized RNA molecule, the primary transcript, is established.
		The spliceosome is a catalytically active complex, which does not need energy for the earliest assembling, but all subsequent assembly steps require NTP hydrolysis.
		The spliceosome is a very complex molecular assembly, and the splicing process includes two main steps and many additional substeps.
	wwwchem.csustan.edu /chem4400/sjbr/brajeno98.htm (2477 words)

	Protein Passport Identified
		Working with graduate student Zhaolan Zhou and postdoctoral fellow Ming-juan Luo, Reed found that Aly is recruited to the spliceosome, an amazingly dynamic complex of proteins in the nucleus that splices pre-messenger RNA, the transcribed form of DNA.
		Since splicing is upstream from export, she began to wonder if the spliceosome was somehow marking spliced mRNA as distinct from the RNA packaged by hnRNPs, and thus safe for export.
		Instead, Aly is found in nuclear "speckles," 20 to 50 localized regions in the cell nucleus that hold the molecular parts for the spliceosome.
	www.hms.harvard.edu /news/releases/0900reed.html (920 words)

	Large-Scale Proteomic Analysis of the Human Spliceosome -- Rappsilber et al. 12 (8): 1231 -- Genome Research
		A mixture of spliceosomal complexes was assembled on biotinylated, radioactively labeled RNA (see Methods).
		Proteins associated with the two different substrates were largely identical, especially for the core spliceosomal components.
		Reed, R. Protein composition of mammalian spliceosomes assembled in vitro.
	www.genome.org /cgi/content/full/12/8/1231 (7068 words)

	AAAS - AAAS News Release
		Saba Valadkhan was born in a small town just outside of Tehran, and with much encouragement from her parents, she excelled in her studies and then entered medical school at an early age.
		At that time, the scientific community knew enough about the spliceosome to sort of figure out who the major players are [within that machinery], but still, nobody could exactly figure out what was going on.
		There was a lot of guessing, but nobody had really been able to pinpoint what was the catalytic part, the part that performs the essential function, and what the other parts were, that perform a supportive role for the core element.
	www.aaas.org /news/releases/2005/0210ys-Valadkhan.shtml (3777 words)

	Nik H. Chmiel - Doudna Research Group, UC Berkeley (Site not responding. Last check: 2007-11-05)
		In addition, alternative splicing of transcripts is used in gene regulation and allows for the production of tissue-specific proteins or those that are needed only for specific stages in the life of an organism.
		Faulty spliceosomal proteins have been linked to cancer as well as diseases such as Huntington's and rheumatoid arthritis.
		While biochemistry has provided a means by which to investigate the interactions of spliceosomal components with target RNA, structural insight into the details of these RNA-protein interactions is lacking.
	rna.berkeley.edu /People/nik.html (387 words)

	The Rockefeller University - Magda Konarska Lab
		Since recognition of the 5´ splice site (5´SS) is required for spliceosome assembly it is important to elucidate the nature and temporal order of interactions between the 5´SS sequence and the spliceosome components.
		The specificity of this association is remarkably similar to that observed in vivo as defined by the 5´SS consensus sequence.
		We have recently demonstrated that the most highly conserved element of the 5´SS consensus, the GU dinucleotide at the 5´ end of the intron is recognized by p220, a protein component of U5 snRNP present in the spliceosome.
	www.rockefeller.edu /labheads/konarska/konarska-lab.php (561 words)

	Recycling of the U12-Type Spliceosome Requires p110, a Component of the U6atac snRNP -- Damianov et al. 24 (4): 1700 -- ...
		Recycling of the U12-Type Spliceosome Requires p110, a Component of the U6atac snRNP -- Damianov et al.
		Splicing of precursors to mRNAs by the spliceosomes, p.
		Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis.
	mcb.asm.org /cgi/content/full/24/4/1700 (5543 words)

	.:IBiS Graduate Program :: Faculty :: Erik J. Sontheimer:.
		The machinery that removes introns from mRNA precursors is a large macromolecular machine called the spliceosome.
		Five small nuclear RNAs (snRNAs) are essential for spliceosome function, and establish a dynamic network of interactions that mediate spliceosome assembly, activation, and catalysis.
		The spliceosome protein Prp8 is very large (~280 kDa) and highly conserved, and genetic analyses suggest that it regulates the RNA structural rearrangements that underlie spliceosome catalysis.
	www.biochem.northwestern.edu /ibis/faculty/sontheimer.htm (688 words)

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