Control of Dead end localization and activity--implications for the function of the protein in antagonizing miRNA function.
Dead end (dnd) is a vertebrate-specific component of the germ plasm and germ-cell granules that is crucial for germ-cell development in zebrafish and mouse. Dnd counteracts the inhibitory function of miRNAs, thereby facilitating the expression of proteins such as Nanos and Tdrd7 in the germ cells. Here, we show that cis-acting elements within dnd mRNA and the RNA recognition motive (RRM) of the protein are essential for targeting protein expression to the germ cells and to the perinuclear granules, respectively. We demonstrate that as it executes its function, Dnd translocates between the germ-cell nucleus and germ-cell granules. This phenomenon is not observed in proteins mutated in the RRM motif, correlating with loss of function of Dnd. Based on molecular modeling, we identify the putative RNA binding domain of Dnd as a canonical RRM and propose that this domain is important for protein subcellular localization and function.
Slanchev
Krasimir
K
Max-Planck-Institute for Biophysical Chemistry, Germ Cell Development, Am Fassberg 11, 37070 Goettingen, Germany.
Stebler
Juerg
J
Goudarzi
Mehdi
M
Cojocaru
Vlad
V
Weidinger
Gilbert
G
Raz
Erez
E
D020413:3' Untranslated Regions / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005854:Germ Cells / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D034443:RNA Transport; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D040681:Structural Homology, Protein; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D020413:3' Untranslated Regions; D035683:MicroRNAs; D016601:RNA-Binding Proteins; D029961:Zebrafish Proteins; C539707:dnd1 protein, zebrafish