Identification of nucleotide patterns enriched in secreted RNAs as putative cis-acting elements targeting them to exosome nano-vesicles.
Identification of nucleotide patterns enriched in secreted RNAs as putative cis-acting elements targeting them to exosome nano-vesicles.
复制标题
DOI：
10.1186/1471-2164-12-s3-s18
复制
发表时间：
2011-11-30
期刊：
影响因子：
4.4
通讯作者：
Kurochkin IV
中科院分区：
文献类型：
--
作者：
Batagov AO;Kuznetsov VA;Kurochkin IV
外泌体是由大多数细胞释放的纳米级膜囊泡。据推测，它们参与细胞间通讯和靶细胞的遗传重编程。除了蛋白质和脂质，它们释放RNA分子，其中许多不存在于供体细胞中，这意味着它们包装到这些囊泡中的高度选择性模式。靶向RNA到囊泡的序列基序目前是未知的。采用从头算方法对富含外泌体的RNA（eRNA）一级序列中潜在的RNA分泌基序进行了计算鉴定。详尽的基序分析首次揭示了eRNA的独特序列特征。我们发现了多个线性基序，特别是丰富的分泌RNA。提出了它们作为靶向RNA至外泌体的顺式作用元件的潜在功能。的图案共定位在相同的成绩单表明这些分泌信号的组合组织。我们研究了所发现的图案与其他RNA参数的关联。分泌的RNA被发现有几乎两倍短的半衰期，平均与细胞质RNA相比，和一些eRNA特异性基序的发生显着相关的eRNA功能。此外，我们发现eRNA高度富集在长的非编码RNA中。分泌的RNA共享特定的序列基序，这些基序可能潜在地充当将RNA靶向至外来体的顺式作用元件。这些模体的发现将有助于我们理解eRNA在细胞间通讯和靶细胞基因重编程中的作用。它还将促进纳米级囊泡工程和选择性靶向感兴趣的RNA到这些囊泡用于基因治疗目的。
Exosomes are nanoscale membrane vesicles released by most cells. They are postulated to be involved in cell–cell communication and genetic reprogramming of their target cells. In addition to proteins and lipids, they release RNA molecules many of which are not present in the donor cells implying a highly selective mode of their packaging into these vesicles. Sequence motifs targeting RNA to the vesicles are currently unknown. Ab initio approach was applied for computational identification of potential RNA secretory motifs in the primary sequences of exosome-enriched RNAs (eRNAs). Exhaustive motif analysis for the first time revealed unique sequence features of eRNAs. We discovered multiple linear motifs specifically enriched in secreted RNAs. Their potential function as cis-acting elements targeting RNAs to exosomes is proposed. The motifs co-localized in the same transcripts suggesting combinatorial organization of these secretory signals. We investigated associations of the discovered motifs with other RNA parameters. Secreted RNAs were found to have almost twice shorter half-life times on average, in comparison with cytoplasmic RNAs, and the occurrence of some eRNA-specific motifs significantly correlated with this eRNA feature. Also, we found that eRNAs are highly enriched in long noncoding RNAs. Secreted RNAs share specific sequence motifs that may potentially function as cis-acting elements targeting RNAs to exosomes. Discovery of these motifs will be useful for our understanding the roles of eRNAs in cell-cell communication and genetic reprogramming of the target cells. It will also facilitate nano-scale vesicle engineering and selective targeting of RNAs of interest to these vesicles for gene therapy purposes.