FIND ARTICLE

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1
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Alternative splicing is a process in which a single pre-mRNA is formed of more than one isoform mRNA. Type nascent mRNA isoform is the result of a fairly complex regulatory mechanisms that allow to obtain , for example, tissue- specific splicing pattern or changes in cellular splicing profile at various stages of development. This is possible thanks to the cooperation of a number of elements , among which are: the nucleotide sequence and secondary structure of pre- mRNA splicing factors and additional factors proteinaceous or nonproteinaceous . In addition to the basic splicing signals ( splice sites , branch point , route polipirymidynowy ) , in pre-mRNA undergoing alternative splicing regulatory elements are located . Here are intronic enhancers (ISE ) and silencers (ISS ) and exon enhancers (ESE ) and silencers ( ESS). Their function in regulation of alternative splicing by binding generally relevant trans acting factors , which in turn affect splice site selection by spliceosom . The secondary structure of pre-mRNA alternative splicing affects deciding on the availability of particles for splicing factors . First, the creation of secondary structure associated with the formation of double-stranded RNA fragments that are recognized by certain trans -acting factors . In addition, the secondary structure of the mutual change in position of the cis-element , which creates additional regulatory opportunities . A fundamental role in the regulation of alternative splicing , however, satisfy the trans -acting factors . These include , among others, the SR and hnRNP proteins . SR proteins bind predominantly to the enhancer sequences acting as splicing activators . The extent of phosphorylation of these proteins varies with the course of splicing , and is subject to complex regulation . HnRNP proteins bind to sequences insulation and are inhibitors of splicing . The best characterized protein is representative of PTB , which - as an inhibitor of splicing - primarily involved in splicing tissue- specific . In fact, the activator and inhibitor proteins act simultaneously splicing , and splicing the formula ultimately determined by the type of bound proteins , their ability to interact with other proteins ( including the spliceosome components ) as well as pozasplicingowe factors . Transcription is the process quite strongly coupled to alternative splicing . The main role is played by RNA polymerase II , and especially its C-terminal domain : CTD . This domain is responsible , inter alia, for the distribution of splicing factors and transcription in the nucleus . Prognostic factors of a number of protein splicing and transcription coupling by adjusting the degree of CTD domain phosphorylation . The functions of RNA polymerase II in splicing are also dependent on the promoter recognized by its transcribed gene. The promoter may in fact determine the capacity of SR protein binding domain or processivity CTD of RNA polymerase II ( polymerase procesywność sometimes affect the course of splicing ) . Mutual splicing and regulation of transcription is achieved by spatial and temporal coupling of the two processes. Splicing is inhibited during mitosis ; This effect is mainly the result of changes in the degree of phosphorylation of certain splicing factors . For example, dephosphorylation is SRp38 protein with the onset of mitosis and in the form of SR protein interferes with an early step of splicing . Phosphorylation of this agent after the completion of mitosis , cell restores the ability to perform splicing . Splicing is regulated by some other processes in the cell. For example, some use a process of splicing factors bearing mRNA to premature stop codon in expression level control , as is the case with the protein PTB . The various kinds of active cell extracellular stimuli such as growth factors, hormones and factors causing depolarization of the cell membrane. One of the cellular response to these stimuli is changing the profile of alternative splicing . Are involved here signaling pathways that alter the degree of phosphorylation of the relevant factors acting in trans ( mainly SR proteins ) . Splicing can be adjusted by placing the cells of certain chemical compounds. These include, low molecular weight inhibitors of splicing - these compounds inhibit splicing at different stages , and some promise involves the use thereof in the treatment of diseases caused by abnormal splicing .

The Editorial Board
Andrzej Łukaszyk - przewodniczący, Zofia Bielańska-Osuchowska, Szczepan Biliński, Mieczysław Chorąży, Aleksander Koj, Włodzimierz Korochoda, Leszek Kuźnicki, Aleksandra Stojałowska, Lech Wojtczak

Editorial address:
Katedra i Zakład Histologii i Embriologii Uniwersytetu Medycznego w Poznaniu, ul. Święcickiego 6, 60-781 Poznań, tel. +48 61 8546453, fax. +48 61 8546440, email: mnowicki@ump.edu.pl

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