Combined functions of two RRMs in Dead ‐end1 mimic helicase activity to promote nanos1 translation in the germline

Dead ‐end1 (Dnd1) is a vertebrate specific RNA‐binding protein essential for germline development. Dnd1 protein contains two putative RNA recognition motifs (RRMs). Here we report that the RRM1 is required for binding its target RNAs, whereas the RRM2 promotes translation through the action of ATPase . Dead ‐end1 (Dnd1) expression is restricted to the vertebrate germline where it is believed to activate translation of messenger RNAs (mRNAs) required to protect and promote that unique lineage.Nanos1 is one such germline mRNA whose translation is blocked by a secondary mRNA structure within the open reading frame  (ORF). Dnd1 contains a canonical RNA recognition motif (RRM1) in its N‐terminus but also contains a less conserved RRM2. Here we provide a mechanistic picture of thenanos1 mRNA –Dnd1 interaction in theXenopus germline. We show that RRM1, but not RRM2, is required for bindingnanos1. Similar to the zebrafish homolog,Xenopus Dnd1 possesses ATPase activity. Surprisingly, this activity appears to be within the RRM2, different from the C ‐terminal region where it is found in zebrafish. More importantly, we show that RRM2 is required fornanos1 translation and germline survival. Further, Dnd1 functions as a homodimer and bindsnanos1 mRNA just downstream of the secondary structure required fornanos1 repression. We propose a model in which the RRM1 is required to bindnanos1 mRNA while the RRM2 is required to promote translation through the action of ATPase. Dnd1 ap...

Source: Molecular Reproduction and Development - October 18, 2018 Category: Reproduction Medicine Authors: Tristan Aguero, Zhigang Jin, Dawn Owens, Arun Malhotra, Karen Newman, Jing Yang, Mary Lou King Tags: RESEARCH ARTICLE Source Type: research