Abstract
F11R is a cell adhesion molecule found on the surface of human platelets. It plays a role in platelet aggregation, cell migration and cell proliferation. F11R is subjected to RNA editing, a post-transcriptional modification which affects RNA structure, stability, localization, translation and splicing. RNA editing in the 3'UTR of F11R and RNA levels are increased upon hypoxia. We therefore set to examine if RNA editing plays a role in the increase of F11R RNA seen upon hypoxic conditions. We show that ADAR1, but not ADAR2, takes part in the editing of F11R however editing alone is not sufficient for obtaining an elevation in RNA levels. In addition we show that hyper-edited mature mRNAs are retained in the nucleus and are associated with p54nrb. We therefore conclude that hypoxia-induced edited RNAs of F11R are preferentially stabilized and accumulate in the nucleus preventing their export to the cytoplasm for translation. This mechanism may be used by additional proteins in the cell as part of the cell's effort to reduce metabolism upon hypoxic stress.
Highlights
The complexity of higher organisms is achieved by a variety of post-transcriptional and post-translational mechanisms that enhance gene and protein diversity through the generation of alternative products from a single gene and by their effects on RNA and protein processing
Silencing of ADAR1 In order to investigate a possible involvement of RNA editing in the regulation of F11 receptor (F11R) expression upon hypoxia, we silenced ADAR1 in the LB cells using a specific siRNA targeted towards a common region in the transcripts of both ADAR1 subunits: p110 and p150
ADAR1 silencing did not alter the elevated levels of F11R mRNA seen upon hypoxia nor did it affect the amount of mRNA in normoxia (Figure 2A)
Summary
The complexity of higher organisms is achieved by a variety of post-transcriptional and post-translational mechanisms that enhance gene and protein diversity through the generation of alternative products from a single gene and by their effects on RNA and protein processing. RNA editing is one of the posttranscriptional mechanisms that introduces changes in RNA sequences allowing organisms to produce many more gene products and functions than predicted based on the number of genes within their genome[1]. RNA editing is an essential process for adequate development and is widespread in mammals [2,3]. Of the various types of RNA editing, the adenosine-to-inosine (A-to-I) base modification is the most widespread in higher eukaryotes affecting gene expression at several levels by targeting different types of transcripts [4]. Very little is known about the molecular pathways that lead to changes in the activity or specificity of the RNA machinery
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
