title: Human minibrain homologue (MNBH/DYRK1): characterization, alternative splicing, differential tissue expression, and overexpression in Down syndrome.
abstract: The human homologue (MNBH/DYRK1) of the Drosophila minibrain gene maps to human chromosome 21 within the Down syndrome (DS) critical region and is within the region minimally deleted in chromosome 21-linked microcephaly. As a first step in gaining insight into the role that MNBH may have in human neurogenesis, and as a lead-up to the development of mouse models for MNBH overexpression, we have characterized the gene at the molecular level. We describe here the MNBH full-length transcript, alternative splicing, expression profile, and genomic organization. The full-length cDNA of MNBH is 5. 2 kb and is composed of 17 exons spanning 150 kb, between markers D21S335 and D21S337. Transcripts MNBHa and MNBHb arise from the use of different first exons in the 5'-UTR and are differentially expressed. MNBHa is expressed ubiquitiously in a broad spectrum of tissues and is apparently under the control of a CpG island. MNBHb is expressed only in heart and skeletal muscle and is apparently under the control of a TATA-like box. Four alternative splicing events affecting the C-terminus of the protein yield at least four isoforms of MNBH (MNBH-iso1, MNBH-iso2, MNBH-iso3, and MNBH-iso4). A PEST sequence, potentially involved in the rapid degradation of the protein, is present in all the isoforms. A histidine repeat and a serine/threonine domain are present only in the largest form of the protein (MNBH-iso1). MNBH was overexpressed 1.5-fold in DS brains and Dyrk1 about 2.1-fold in the brains of the Ts65Dn mice. The information provided here should be valuable for MNBH mutation studies and aid in the development of DS animal models.
mesh_terms: D020413:3' Untranslated Regions; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D018076:DNA, Complementary; D004314:Down Syndrome / Q000235:genetics*; D015870:Gene Expression; D014644:Genetic Variation; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics*; D017433:Protein Structure, Secondary; D011505:Protein-Tyrosine Kinases; D012333:RNA, Messenger; D014158:Transcription, Genetic; D000097603:Dyrk Kinases