Nuclease escape elements protect messenger RNA against cleavage by multiple viral endonucleases

Mandy Muller; Britt A. Glaunsinger

The IL-6 and GADD45B SREs display relatively limited sequence similarity but have 338 at least one structurally important stem-loop in common. Thus, RNA structure appears to 339 be a central component of an SRE and is likely to influence recruitment or arrangement of 340 proteins involved in escape. This is in line with the fact that RNP assembly can be more 341 heavily impacted by structural fidelity than primary sequence recognition [59]. We 342 hypothesize that there is a core set of proteins required for SRE function, such as HuR, but 343 that individual SREs recruit distinct accessory factors that dictate the conditions or 344 mechanism by which that SRE protects against nuclease targeting. In this regard, we have 345 not found significant overlap between known HuR mRNA targets and mRNAs that are not 346 downregulated by SOX [22] . This is in agreement with the fact that many of the SRE bound 347 proteins have a breadth of roles in controlling RNA fate beyond conferring nuclease escape 348