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福彩快乐十分中奖规则:Component of splicing factor SF3b plays a key role in translational control of polyribosomes on the endoplasmic reticulum
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p180/RRBP1 is an essential factor for high-rate protein synthesis on the endoplasmic reticulum (ER) in terminally differentiated secretory cells. A unique system for selectively enhanced translation has been proposed for p180-associated polyribosomes. Here we provide evidence that SF3b4, an RNA-binding protein in the splicing factor, plays a key and unexpected role in translation control as a cofactor for p180. It appears that abundant expression of both SF3b4 and p180 is critical for increased ER mRNA targeting, and consequently leads to the heavy polyribosome assembly. This discovery could shed light on the pathogenesis of Nager syndrome caused by SF3B4 mutation, as such mutations may result in abnormal collagen biosynthesis, potentially affecting bone morphogenesis in patients with this disease.
One of the morphological hallmarks of terminally differentiated secretory cells is highly proliferated membrane of the rough endoplasmic reticulum (ER), but the molecular basis for the high rate of protein biosynthesis in these cells remains poorly documented. An important aspect of ER translational control is the molecular mechanism that supports efficient use of targeted mRNAs in polyribosomes. Here, we identify an enhancement system for ER translation promoted by p180, an integral ER membrane protein we previously reported as an essential factor for the assembly of ER polyribosomes. We provide evidence that association of target mRNAs with p180 is critical for efficient translation, and that SF3b4, an RNA-binding protein in the splicing factor SF3b, functions as a cofactor for p180 at the ER and plays a key role in enhanced translation of secretory proteins. A cis-element in the 5′ untranslated region of collagen and fibronectin genes is important to increase translational efficiency in the presence of p180 and SF3b4. These data demonstrate that a unique system comprising a p180–SF3b4–mRNA complex facilitates the selective assembly of polyribosomes on the ER.
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Author contributions: T.U. and K.O.-G. designed research; T.U. and Y.T. performed research; T.U., Y.T., and K.O.-G. analyzed data; and T.U., Y.T., R.Y., A.M., S.H., and K.O.-G. wrote the paper.
Conflict of interest statement: T.U., Y.T., and K.O.-G. are coinventors of patent applications based on this work. T.U., Y.T., S.H., and K.O.-G. are employees of Nippi, Inc., an applicant of the patents (JP58488 and other related patent applications, including in the European Union and the United States). Nippi, Inc. is going to develop application of a new engineering technology (spERt Technology) based on ideas described in this study, which is likely to up-regulate productivity of recombinant proteins. Our development of spERt Technology has not influenced any conclusions of this study.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1901742116/-/DCSupplemental.
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