NUCLEOTIDE-SEQUENCE OF THE RING3 GENE IN THE CLASS-II REGION OF THE MOUSE MHC AND ITS ABUNDANT EXPRESSION IN TESTICULAR GERM-CELLS

The RING3 (NAT) gene is the first and only locus with no obvious funct ion associated with the immune system in the class II region of the hu man major histocompatibility complex. This gene is a homologue of the Drosophila homeotic gene female sterile homeotic (fsh) and encodes a n uclear serine-threonine kinase. To study more about the physiological function of the RING3 gene, we isolated a mouse homologue from a genom ic library, determined its gene structure, and investigated its expres sion profile. The mouse Ring3 gene spans approximately 8 kb and consis ts of 12 exons encoding a 798-amino-acid protein, sharing as high as 9 6% amino acid identity with the human RING3 protein. Northern hybridiz ation revealed that the Ring3 gene abundantly produced 3.8- and 3.0-kb transcripts in the testis but was weakly expressed with 4.6- and 3.8- kb transcripts in somatic tissues. It appears that testis-specific 3.0 -kb transcript gives rise to a smaller size Ring3 protein resulting fr om the usage of the second ATG codon for translational initiation comp ared to the almost ubiquitous 4.6-kb transcript. In RNAs isolated from fractionated testicular germ cells, the two testicular mRNAs were det ected exclusively in the fractions containing a large population of ro und spermatids and pachytene spermatocytes. Furthermore, in situ hybri dization on cross sections of seminiferous tubules in the testis showe d that the expression of the Ring3 gene was initiated at the pachytene spermatocyte stage during meiosis and persisted throughout the round spermatid stage during spermiogenesis. These results suggest that the Ring3 gene plays an important role in spermatogenesis. (C) 1998 Academ ic Press.