Multiple features contribute to efficient constitutive splicing of an unusually large exon
Multiple features contribute to efficient constitutive splicing of an unusually large exon
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DOI：
10.1093/nar/29.11.2292
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发表时间：
2001-06-01
影响因子：
14.9
通讯作者：
Peterson, ML
中科院分区：
文献类型：
--
作者：
Bruce, SR;Peterson, ML
脊椎动物的内部外显子长度通常在50和400 nt之间;超出此大小范围的外显子可能需要额外的外显子和/或内含子序列才能剪接到成熟mRNA中。小鼠多聚免疫球蛋白受体基因具有654 nt的外显子，其被有效地剪接到mRNA中。以前没有研究过大的组成型外显子。我们发现，强的5'剪接位点是该外显子被完整剪接所必需的，但是单独的剪接位点不足以有效地剪接大外显子。至少两个外显子序列和一个进化上保守的内含子序列也有助于识别该外显子。然而，这些元件具有冗余的活性，因为它们只能与降低剪接效率的其他突变一起检测，几个突变激活了产生较小外显子的隐蔽5'剪接位点。因此，这些潜在位点和真实5'剪接位点的使用之间的平衡必须分别通过抑制或增强这些位点的使用的序列来调节。此外，增强隐蔽剪接位点使用的序列必须不存在于该大外显子中。
Vertebrate internal exons are usually between 50 and 400 nt long; exons outside this size range may require additional exonic and/or intronic sequences to be spliced into the mature mRNA, The mouse polymeric immunoglobulin receptor gene has a 654 nt exon that is efficiently spliced into the mRNA, We have examined this exon to identify features that contribute to its efficient splicing despite its large size; a large constitutive exon has not been studied previously. We found that a strong 5' splice site is necessary for this exon to be spliced intact, but the splice sites alone were not sufficient to efficiently splice a large exon, At least two exonic sequences and one evolutionarily conserved intronic sequence also contribute to recognition of this exon, However, these elements have redundant activities as they could only be detected in conjunction with other mutations that reduced splicing efficiency, Several mutations activated cryptic 5' splice sites that created smaller exons, Thus, the balance between use of these potential sites and the authentic 5' splice site must be modulated by sequences that repress or enhance use of these sites, respectively. Also, sequences that enhance cryptic splice site use must be absent from this large exon.