FUNCTION OF CONSERVED DOMAINS OF HNRNP A1 AND OTHER HNRNP A/B PROTEINS
FUNCTION OF CONSERVED DOMAINS OF HNRNP A1 AND OTHER HNRNP A/B PROTEINS
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DOI：
10.1002/j.1460-2075.1994.tb06883.x
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发表时间：
1994-11-15
期刊：
影响因子：
11.4
通讯作者：
KRAINER, AR
中科院分区：
文献类型：
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作者：
MAYEDA, A;MUNROE, SH;KRAINER, AR
HnRNP A1是一种前mRNA结合蛋白，能拮抗剪接因子SF2/ASF或SC35的选择性剪接活性，导致远端5‘剪接位点的激活。通过对重组人hnRNP A1的突变，确定了hnRNP A1功能的结构要求。在两个RNA识别基序的RNP-1亚基中，两个保守的Phe残基似乎参与了特定的RNA-蛋白质相互作用，并对调节选择性剪接至关重要。这些残基不是一般的前mRNA结合或RNA退火活性所必需的。C-末端富含甘氨酸的结构域是选择性剪接活性、稳定的RNA结合和最佳RNA退火活性所必需的。HnRNP A1(B)是hnRNP A1的一种选择性剪接异构体，具有较长的富含甘氨酸的结构域，与前mRNA结合更强，但选择性剪接活性有限。相反，hnRNP A2和B1与hnRNP A1的氨基酸同源性为68%，与前mRNA结合更弱，剪接位点转换活性强于hnRNP A1。我们认为，拮抗hnRNP A/B和SR蛋白的特定组合参与调节细胞前mRNAs不同亚集的选择性剪接。
hnRNP A1 is a pre-mRNA binding protein that antagonizes the alternative splicing activity of splicing factors SF2/ASF or SC35, causing activation of distal 5' splice sites. The structural requirements for hnRNP A1 function were determined by mutagenesis of recombinant human hnRNP A1. Two conserved Phe residues in the RNP-1 submotif of each of two RNA recognition motifs appear to be involved in specific RNA-protein interactions and are essential for modulating alternative splicing. These residues are not required for general pre-mRNA binding or RNA annealing activity. The C-terminal Gly-rich domain is necessary for alternative splicing activity, for stable RNA binding and for optimal RNA annealing activity. hnRNP A1(B), which is an alternatively spliced isoform of hnRNP A1 with a longer Gly-rich domain, binds more strongly to pre-mRNA but has only limited alternative splicing activity. In contrast, hnRNP A2 and B1, which have 68% amino acid identity with hnRNP A1, bind more weakly to pre-mRNA and have stronger splice site switching activities than hnRNP A1. We propose that specific combinations of antagonistic hnRNP A/B and SR proteins are involved in regulating alternative splicing of distinct subsets of cellular pre-mRNAs.