英语翻译

这是一个RNA剪切时的复合体结构.你看一下下面的详细解说就能理解了：
The model for formation of the spliceosome active site involves an ordered,stepwise assembly of discrete snRNP particles on the hnRNA substrate.The first recognition of hnRNAs involves U1 snRNP binding to the 5' end splice site of the hnRNA and other non-snRNP associated factors to form the commitment complex,or early (E) complex in mammals.[8][9] The commitment complex is an ATP-independent complex that commits the hnRNA to the splicing pathway.[10] U2 snRNP is recruited to the branch region through interactions with the E complex component U2AF (U2 snRNP auxiliary factor) and possibly U1 snRNP.In an ATP-dependent reaction,U2 snRNP becomes tightly associated with the branch point sequence (BPS) to form complex A.A duplex formed between U2 snRNP and the hnRNA branch region bulges out the branch adenosine specifying it as the nucleophile for the first transesterification.[11]
The presence of a pseudouridine residue in U2 snRNA,nearly opposite of the branch site,results in an altered conformation of the RNA-RNA duplex upon the U2 snRNP binding.Specifically,the altered structure of the duplex induced by the pseudouridine places the 2' OH of the bulged adenosine in a favorable position for the first step of splicing.[12] The U4/U5/U6 tri-snRNP (see Figure 1) is recruited to the assembling spliceosome to form complex B,and following several rearrangements,complex C (the spliceosome) is activated for catalysis.[13][14] It is unclear how the triple snRNP is recruited to complex A,but this process may be mediated through protein-protein interactions and/or base pairing interactions between U2 snRNA and U6 snRNA.
The U5 snRNP interacts with sequences at the 5' and 3' splice sites via the invariant loop of U5 snRNA[15] and U5 protein components interact with the 3' splice site region.[16]
Upon recruitment of the triple snRNP,several RNA-RNA rearrangements precede the first catalytic step and further rearrangements occur in the catalytically active spliceosome.Several of the RNA-RNA interactions are mutually exclusive; however,it is not known what triggers these interactions,nor the order of these rearrangements.The first rearrangement is probably the displacement of U1 snRNP from the 5' splice site and formation of a U6 snRNA interaction.It is known that U1 snRNP is only weakly associated with fully formed spliceosomes,[17] and U1 snRNP is inhibitory to the formation of a U6-5' splice site interaction on a model of substrate oligonucleotide containing a short 5' exon and 5' splice site.[18] Binding of U2 snRNP to the branch point sequence (BPS) is one example of an RNA-RNA interaction displacing a protein-RNA interaction.Upon recruitment of U2 snRNP,the branch binding protein SF1 in the commitment complex is displaced since the binding site of U2 snRNA and SF1 are mutually exclusive events.
Within the U2 snRNA,there are other mutually exclusive rearrangements that occur between competing conformations.For example,in the active form,stem loop IIa is favored; in the inactive form a mutually exclusive interaction between the loop and a downstream sequence predominates.[14] It is unclear how U4 is displaced from U6 snRNAm,although RNA has been implicated in spliceosome assembly,and may function to unwind U4/U6 and promote the formation of a U2/U6 snRNA interaction.The interactions of U4/U6 stem loops I and II dissociate and the freed stem loop II region of U6 folds on itself to form an intramolecular stem loop and U4 is no longer required in further spliceosome assembly.The freed stem loop I region of U6 base pairs with U2 snRNA forming the U2/U6 helix I.However,the helix I structure is mutually exclusive with the 3' half of an internal 5' stem loop region of U2 snRNA.