Novel Staufen splicing suggests physiological regulation of mRNA transport in oligodendrocytes.

MARTÍNEZ TOSAR LJ, BULLOJ A, SANTA COLOMA TA AND BOCCACCIO GL.

Villa Carlos Paz – Córdoba

Congreso; XXXVII Reunión Anual SAIB; 2001

SAIB

<!-- /* Font Definitions */ @font-face {font-family:"Cambria Math"; panose-1:2 4 5 3 5 4 6 3 2 4; mso-font-charset:0; mso-generic-font-family:roman; mso-font-pitch:variable; mso-font-signature:-1610611985 1107304683 0 0 159 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-unhide:no; mso-style-qformat:yes; mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; mso-bidi-font-size:10.0pt; font-family:"Arial","sans-serif"; mso-fareast-font-family:"Times New Roman"; mso-bidi-font-family:"Times New Roman"; mso-ansi-language:ES; mso-fareast-language:ES;} .MsoChpDefault {mso-style-type:export-only; mso-default-props:yes; font-size:10.0pt; mso-ansi-font-size:10.0pt; mso-bidi-font-size:10.0pt;} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> Cytoplasmic mRNA transport is an important cell strategy to achieve protein localization to different subcellular domains. Among the many RNA binding proteins described to date, Staufen has gathered special attention due to its widespread presence as well as to its remarkable homology in many different species. Staufen is an RNA binding protein originally described in Drosophila, with several double stranded RNA binding domains (dsRBDs). We propose that Staufen is involved in the sorting of mRNA encoding for Myelin Basic Protein (MBP) in oligodendrocytes through the formation of a transport complex. In this cell type, MBP is required for the correct assembly of the myelin sheath that enwraps axons. Here we report three novel alternative splicing isoforms by RT-PCR, cloning and sequence analysis. One of these variants, has a 6-aminoacid insertion in dsRBD3, the RBD with strongest affinity for RNA, suggesting differential RNA binding properties for this isoform. Accordingly, other authors have recently shown this variant to have a diminished RNA binding capacity. Another isoform, bears a frameshift which should give rise to an novel domain with unknown function. Alternatively, a premature stop codon present 76 bases upstream the last exon junction makes it a putative target for Non-sense Mediated Decay, a mechanism which degrades mRNAs with this profile. Both of these isoforms pose new points for phisiological regulation of Staufen expression/function and ultimately, of the mRNA transport process.