剪接是通過將被稱為“內(nèi)含子”的RNA片段除掉來從大前體分子(pre-mRNA)生成信使RNA (mRNA)的過程，該過程由被稱為snRNP的“蛋白-RNA復(fù)合物”完成,。一個(gè)剪接體含有相同數(shù)量的U1、 U2,、U4,、U5和U6 snRNP,，但U1 snRNP水平遠(yuǎn)遠(yuǎn)超過剪接體所需水平，從而導(dǎo)致這樣的觀點(diǎn)：“多余”的U1也許有獨(dú)立于剪接的功能?，F(xiàn)在,，一個(gè)這樣的功能已被發(fā)現(xiàn)，它涉及U1 snRNA和一些pre-mRNA之間的相互作用,，后者含有帶“多腺苷酸化”點(diǎn)的“內(nèi)含子”,。這可通過防止過早終止及“多腺苷酸化”來保護(hù)新生成的pre-mRNA不受損傷。（生物谷Bioon.com）
生物谷推薦原文出處：
Nature doi:10.1038/nature09479
U1 snRNP protects pre-mRNAs from premature cleavage and polyadenylation
Daisuke Kaida1, Michael G. Berg1, Ihab Younis1, Mumtaz Kasim1, Larry N. Singh1, Lili Wan1 & Gideon Dreyfuss1
Howard Hughes Medical Institute, Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6148, USA
Correspondence to: Gideon Dreyfuss1 Email: [email protected]
Top of pageAbstractIn eukaryotes, U1 small nuclear ribonucleoprotein (snRNP) forms spliceosomes in equal stoichiometry with U2, U4, U5 and U6 snRNPs; however, its abundance in human far exceeds that of the other snRNPs. Here we used antisense morpholino oligonucleotide to U1 snRNA to achieve functional U1 snRNP knockdown in HeLa cells, and identified accumulated unspliced pre-mRNAs by genomic tiling microarrays. In addition to inhibiting splicing, U1 snRNP knockdown caused premature cleavage and polyadenylation in numerous pre-mRNAs at cryptic polyadenylation signals, frequently in introns near (<5?kilobases) the start of the transcript. This did not occur when splicing was inhibited with U2 snRNA antisense morpholino oligonucleotide or the U2-snRNP-inactivating drug spliceostatin A unless U1 antisense morpholino oligonucleotide was also included. We further show that U1 snRNA–pre-mRNA base pairing was required to suppress premature cleavage and polyadenylation from nearby cryptic polyadenylation signals located in introns. These findings reveal a critical splicing-independent function for U1 snRNP in protecting the transcriptome, which we propose explains its overabundance.
