Human protein secretory pathway genes are expressed in a tissue-specific pattern to match processing demands of the secretome.
Human protein secretory pathway genes are expressed in a tissue-specific pattern to match processing demands of the secretome.
复制标题
DOI：
10.1038/s41540-017-0021-4
复制
发表时间：
2017
影响因子：
4
通讯作者：
Nielsen J
中科院分区：
文献类型：
--
作者：
Feizi A;Gatto F;Uhlen M;Nielsen J
真核细胞中的蛋白质分泌途径负责传递功能性分泌蛋白。这一通路的功能障碍会导致从先天性疾病到癌症等一系列重要的人类疾病。尽管在分子生物学和生物化学水平上积累了大量的知识，但分泌途径基因的组织特异性表达还没有在转录组水平上进行分析。根据最近的RNA测序研究，组织特异性转录组的最大部分编码分泌组(分泌蛋白)。在这里，问题出现了，如果分泌途径基因的表达水平具有组织特异性的调节。在这项研究中，我们通过对最近发表的人类组织转录组数据进行荟萃分析来解决这个问题。结果，我们检测到68个被称为“极端基因”的基因，它们在分泌途径的特定基因家族中表现出不寻常的表达模式。我们还检查了检测到的极端基因和相应组织丰富的分泌组之间的潜在功能联系。结果，检测到的极端基因与每个组织分泌体中特定翻译后修饰的性质和数量的丰富有关。我们的发现协调了蛋白质分泌途径的内务和组织特异性，我们将其归因于对定义的基因家族的微调调节，以支持分泌蛋白质及其修饰的多样性。分泌途径是人类细胞中普遍存在的一种细胞机制，这里显示出具有组织特异性的特征。查尔默斯理工大学的延斯·尼尔森教授领导的一个研究小组对分泌途径组成部分的基因表达进行了荟萃分析。他们发现，尽管这些成分中的大多数在所有组织中都有表达，但也有不同的成分有微调的表达。他们进一步评估了检测到的调谐和制造一组组织特异性蛋白质(如内分泌系统激素或其受体)所需的过程之间的功能联系。这些发现为了解人类组织中分泌途径的功能开辟了一条新的途径，可能应用于提高药物蛋白的产量，并更深入地了解糖尿病等与内分泌系统有关的疾病的潜在机制。
Protein secretory pathway in eukaryal cells is responsible for delivering functional secretory proteins. The dysfunction of this pathway causes a range of important human diseases from congenital disorders to cancer. Despite the piled-up knowledge on the molecular biology and biochemistry level, the tissue-specific expression of the secretory pathway genes has not been analyzed on the transcriptome level. Based on the recent RNA-sequencing studies, the largest fraction of tissue-specific transcriptome encodes for the secretome (secretory proteins). Here, the question arises that if the expression levels of the secretory pathway genes have a tissue-specific tuning. In this study, we tackled this question by performing a meta-analysis of the recently published transcriptome data on human tissues. As a result, we detected 68 as called “extreme genes” which show an unusual expression pattern in specific gene families of the secretory pathway. We also inspected the potential functional link between detected extreme genes and the corresponding tissues enriched secretome. As a result, the detected extreme genes showed correlation with the enrichment of the nature and number of specific post-translational modifications in each tissue’s secretome. Our findings conciliate both the housekeeping and tissue-specific nature of the protein secretory pathway, which we attribute to a fine-tuned regulation of defined gene families to support the diversity of secreted proteins and their modifications. The secretory pathway, an ubiquitous cellular machinery in human cells, is here shown to have tissue-specific characteristics. A research team led by Prof. Jens Nielsen at the Chalmers University of Technology performed a meta-analysis of the gene expressions of the secretory pathway’ component. They detected that even though most of these components are expressed in all tissues, there exist distinct components with fine-tuned expression. They further evaluated the functional link between the detected tuning and the processes that are demanded to make a set of tissue-specific proteins such as endocrine system hormones or their receptors. These findings open up a new avenue to understand the function of the secretion pathway in human tissues with possible applications for improving production of pharmaceutical proteins and getting more insight into the mechanisms underlying diseases such as diabetes that are connected with the endocrine system.
登录
查看更多内容
影响因子：
5.6
作者：
Pereira-Leal, JB;Seabra, MC
通讯作者：
Seabra, MC
影响因子：
5.8
作者：
Gu, Zuguang;Eils, Roland;Schlesner, Matthias
通讯作者：
Schlesner, Matthias
影响因子：
64.5
作者：
NOVICK, P;FIELD, C;SCHEKMAN, R
通讯作者：
SCHEKMAN, R
影响因子：
3.9
作者：
Donaldson, JG;Honda, A
通讯作者：
Honda, A
影响因子：
56.9
作者：
RODRIGUEZBOULAN, E;NELSON, WJ
通讯作者：
NELSON, WJ