U1 snRNP protects pre-mRNAs from premature cleavage and polyadenylation.
U1 snRNP protects pre-mRNAs from premature cleavage and polyadenylation.
复制标题
作者：
在高等真核生物中，U1 snRNP与U2、U4、U5和U6形成剪接体的化学计量相等，但其丰度远远超过其他snRNP。在此，我们利用反义morpholino oligonucleotide （AMO）对HeLa细胞中的U1 snRNP进行功能性敲低，并通过基因组平铺微阵列鉴定了积累的未剪接前mrna。值得注意的是，除了抑制剪接外，U1 snRNP敲低导致许多pre- mrna在隐聚腺苷化信号（PASs）处过早切割和聚腺苷化（PCPA），通常发生在转录物起始（< 5kb）的内含子处。当使用U2 snRNA AMO或U2 snRNP灭活药物剪接抑素A抑制剪接时，除非还包括U1 AMO，否则不会发生这种情况。我们进一步证明，U1 snRNA-pre-mRNA碱基配对是抑制内含子附近的隐型PASs的PCPA所必需的。这些发现揭示了U1 snRNP在保护转录组方面具有关键的剪接无关功能，我们认为这可以解释它的过量。
In higher eukaryotes, U1 snRNP forms spliceosomes in equal stoichiometry with U2, U4, U5 and U6, however its abundance far exceeds that of the other snRNPs. Here, we used antisense morpholino oligonucleotide (AMO) to U1 snRNA for functional U1 snRNP knockdown in HeLa cells and identified accumulated unspliced pre-mRNAs by genomic tiling microarrays. Remarkably, in addition to inhibiting splicing, U1 snRNP knockdown caused premature cleavage and polyadenylation (PCPA) in numerous pre-mRNAs at cryptic polyadenylation signals (PASs), frequently in introns near (< 5 kb) the start of the transcript. This did not occur when splicing was inhibited with U2 snRNA AMO or the U2 snRNP inactivating drug, spliceostatin A, unless U1 AMO was also included. We further show that U1 snRNA-pre-mRNA base pairing was required to suppress PCPA from nearby cryptic PASs located in introns. These findings reveal a critical splicing-independent function for U1 snRNP in protecting the transcriptome, which we propose explains its overabundance.
登录
查看更多内容
影响因子：
64.5
作者：
LEFEBVRE, S;BURGLEN, L;MELKI, J
通讯作者：
MELKI, J
影响因子：
14.9
作者：
Millevoi S;Vagner S
通讯作者：
Vagner S
影响因子：
16
作者：
Gunderson, SI;Polycarpou-Schwarz, M;Mattaj, IW
通讯作者：
Mattaj, IW
DOI：
10.1073/pnas.1332669100
发表时间：
2003-07-08
影响因子：
11.1
作者：
Fortes, P;Cuevas, Y;Gunderson, SI
通讯作者：
Gunderson, SI
影响因子：
64.5
作者：
Koenig, Harald;Matter, Nathalie;Mueller, Ferenc
通讯作者：
Mueller, Ferenc