Gene expression: The end of the message and beyond
Gene expression: The end of the message and beyond
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基因表达:信息的终结及其他
DOI:
10.1038/307412a0
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发表时间:
1984
期刊:
影响因子:
64.8
通讯作者:
N. Proudfoot
中科院分区:
文献类型:
--
作者:
N. Proudfoot
SINCE last reviewed in these columns a little over a year ago 1, several major steps forward have been made in understanding how the 3'ends of eukaryotic mRNA are formed. First and foremost, histone genes have joined other eukaryotic RNA polymerase II genes in generating their 3'ends not by simple termination of transcription, but by termination followed by post-transcriptional cleavage. The activity responsible for this process has been nearly purified and looks very much like a small nuclear riboprotein or'snurp', not the UI snurp responsible for intron splicing, but another as yet unidentified one. Second, mutation of the AAUAAA conserved sequence found at the 3'ends of poly (A) containing mRNAs has been shown to cause elongation of the mRNA transcript2. This formally proves that the AAUAAA sequence is required for mRNA 3'end formation, and strongly suggests that the sequence is a signal for endonucleolitic cleavage. Finally, the feeling that RNA polymerase II must have a precise termination process, rather than just falling off the gene template at random, has been virtually proven, at least for the mouse {J major globin gene.Max Birnstiel's laboratory in Zurich has been working on the transcription of sea urchin histone genes by injecting them, together or separately, into Xenopus oocytes3. 4. Not surprisingly, several of the activities necessary for the generation of sea urchin histone mRNA are absent in oocytes. Birnstiel's group therefore tried co-injecting sea urchin extracts along with the histone genes to complement the oocyte transcriptional apparatus5 and found that with the extracts, histone gene H3 does generate mRNA that terminates at the correct 3'position, while without the extracts it does not. Purification of the activity using this complementation factor assay6 has now revealed that it is a nuclear RNA-protein complex known affectionately as a'snurp'. Indeed, even a 60-nucleotide RNA fraction free of protein stimulates the production of correct histone mRNA 3'ends when injected along with the histone gene into oocytes-presumably oocytes can package the RNA into a snurp7. Although this group's experiments strongly imply that histone mRNA 3'ends are generated by endonucleolitic cleavage, the final proof has come from other work. Krieg and Melton of Harvard University8 took a different histone gene, placed it under the influence of a bacteriophage (SP6) promoter9, and synthesized in vitro transcripts extending beyond the 3'