The signal sequence coding region promotes nuclear export of mRNA.
The signal sequence coding region promotes nuclear export of mRNA.
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DOI：
10.1371/journal.pbio.0050322
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发表时间：
2007-12
期刊：
影响因子：
9.8
通讯作者：
Rapoport TA
中科院分区：
文献类型：
--
作者：
Palazzo AF;Springer M;Shibata Y;Lee CS;Dias AP;Rapoport TA
在真核细胞中，大多数mrna通过转录输出（TREX）复合体从细胞核中输出，该复合体在mrna剪接和capping后装载到mrna上。我们已经在哺乳动物细胞中研究了编码分泌蛋白的mrna的核输出，这些蛋白通过疏水信号序列靶向内质网膜。将mrna注射到细胞核中或从注射或转染的DNA中合成，然后通过荧光原位杂交将其输出。我们惊奇地发现，信号序列编码区（SSCR）可以作为缺乏内含子或功能帽的mRNA的核输出信号。甚至含有内含子的天然mRNA的输出也被其SSCR增强。与传统的输出一样，ssr依赖途径需要TAP因子，但TREX成分的消耗仅具有中等影响。脊椎动物的SSCR输出信号似乎以腺嘌呤含量低为特征，这一点在全基因组序列分析和SSCR沉默腺嘌呤突变的抑制作用中得到了证实。ssr介导途径的发现解释了先前注意到的信号序列中的氨基酸偏倚，并表明核输出与mrna的膜靶向之间存在联系。在真核细胞中，信使rna （mrna）的前体在细胞核中合成和加工。在加工过程中，非编码内含子被剪接出来，并分别在转录本的开头和结尾添加一个帽和多腺苷序列。由此产生的成熟mRNA通过核孔从细胞核输出到细胞质。内含子和帽都有助于招募mRNA核输出所必需的因子。在这里，我们为一种新的mRNA输出途径提供了证据，该途径对编码分泌蛋白的转录本具有特异性。这些蛋白质含有信号序列，这些信号序列针对它们在内质网膜上进行易位。我们惊奇地发现，信号序列编码区（SSCR）可以作为缺乏内含子或功能帽的mRNA的核输出信号。甚至含有内含子的天然mRNA的输出也被其SSCR增强。在脊椎动物中，SSCR输出信号的特征似乎是腺嘌呤含量低。我们发现的ssr介导的通路解释了先前注意到的信号序列中的氨基酸偏倚，并表明核输出与mrna的膜靶向之间存在联系。信号序列将新合成的分泌蛋白靶向内质网，由腺嘌呤缺失核苷酸序列编码，促进mrna的核输出。
In eukaryotic cells, most mRNAs are exported from the nucleus by the transcription export (TREX) complex, which is loaded onto mRNAs after their splicing and capping. We have studied in mammalian cells the nuclear export of mRNAs that code for secretory proteins, which are targeted to the endoplasmic reticulum membrane by hydrophobic signal sequences. The mRNAs were injected into the nucleus or synthesized from injected or transfected DNA, and their export was followed by fluorescent in situ hybridization. We made the surprising observation that the signal sequence coding region (SSCR) can serve as a nuclear export signal of an mRNA that lacks an intron or functional cap. Even the export of an intron-containing natural mRNA was enhanced by its SSCR. Like conventional export, the SSCR-dependent pathway required the factor TAP, but depletion of the TREX components had only moderate effects. The SSCR export signal appears to be characterized in vertebrates by a low content of adenines, as demonstrated by genome-wide sequence analysis and by the inhibitory effect of silent adenine mutations in SSCRs. The discovery of an SSCR-mediated pathway explains the previously noted amino acid bias in signal sequences and suggests a link between nuclear export and membrane targeting of mRNAs. In eukaryotic cells, precursors of messenger RNAs (mRNAs) are synthesized and processed in the nucleus. During processing, noncoding introns are spliced out, and a cap and poly-adenosine sequence are added to the beginning and end of the transcript, respectively. The resulting mature mRNA is exported from the nucleus to the cytoplasm by crossing the nuclear pore. Both the introns and the cap help to recruit factors that are necessary for nuclear export of an mRNA. Here we provide evidence for a novel mRNA export pathway that is specific for transcripts coding for secretory proteins. These proteins contain signal sequences that target them for translocation across the endoplasmic reticulum membrane. We made the surprising observation that the signal sequence coding region (SSCR) can serve as a nuclear export signal of an mRNA that lacks an intron or functional cap. Even the export of an intron-containing natural mRNA was enhanced by its SSCR. The SSCR export signal appears to be characterized in vertebrates by a low content of adenines. Our discovery of an SSCR-mediated pathway explains the previously noted amino acid bias in signal sequences, and suggests a link between nuclear export and membrane targeting of mRNAs. Signal sequences, which target newly synthesized secretory proteins to the endoplasmic reticulum, are encoded by adenine-depleted nucleotide sequences that promote the nuclear export of the mRNAs.
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影响因子：
4.8
作者：
Blevins, MB;Smith, AM;Powers, MA
通讯作者：
Powers, MA
DOI：
10.1073/pnas.0400933101
发表时间：
2004-03-23
影响因子：
11.1
作者：
Ferraiuolo, MA;Lee, CS;Sonenberg, N
通讯作者：
Sonenberg, N
影响因子：
64.5
作者：
Cheng, Hong;Dufu, Kobina;Reed, Robin
通讯作者：
Reed, Robin
DOI：
10.1083/jcb.104.2.189
发表时间：
1987-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Finlay DR;Newmeyer DD;Price TM;Forbes DJ
通讯作者：
Forbes DJ
影响因子：
64.5
作者：
Brodersen, DE;Clemons, WM;Ramakrishnan, V
通讯作者：
Ramakrishnan, V