RNA recognition motif-type RNA-binding domain containing proteins (RBDPs) participate in RNA metabolism including regulating mRNA stability, nuclear-cytoplasmic shuttling, and splicing. Rbm45 is an RBDP first cloned from rat brain and expressed spatiotemporally during rat neural development. More recently, RBM45 has been associated with pathological aggregates in the human neurological disorders amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and Alzheimer’s. Rbm45 and the neural developmental protein musashi-1 are in the same family of RDBPs and have similar expression patterns. In contrast to Musashi-1, which is upregulated during colorectal carcinogenesis, we found no association of RBM45 overexpression in human colon cancer tissue. In order to begin characterizing RNA-binding partners of Rbm45, we have successfully cloned and expressed human RBM45 in an Intein fusion-protein expression system. Furthermore, to gain a better understanding of the molecular genetics and evolution of Rbm45, we used an in silico approach to analyze the gene structure of the human and mouse Rbm45 homologues and explored the evolutionary conservation of Rbm45 in metazoans. Human RBM45 and mouse Rbm45 span ~17 kb and 13 kb, respectively, and contain 10 exons, one of which is non-coding. Both genes have TATA-less promoters with an initiator and a GC-rich element. Downstream of exon 10, both homologues have canonical polyadenylation signals and an embryonic cytoplasmic polyadenylation element. Moreover, our data indicate Rbm45 is conserved across all metazoan taxa from sponges (phylum Porifera) to humans (phylum Chordata), portending a fundamental role in metazoan development.

Neurodegenerative disorders are caused by the progressive loss of the structure and/or function of neurons, often through cell death, contributing significantly to morbidity and mortality. Cytoplasmic aggregation of proteins into inclusion bodies is a pathological characteristic of amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and Alzheimer’s disorder (AD). These inclusion bodies have been shown to contain RNA-binding proteins participating in RNA-dependent and RNA–independent protein:protein interactions. RNA-binding motif protein 45 (RBM45), also known as developmentally regulated RNA-binding protein-1 (Drbp1), was first identified as a novel RNA binding protein in rat that functions in neural development. Advancing research has indicated a connection between the presence of human RBM45 protein cytosolic aggregates and degenerative neurological diseases. This review considers the structure, function, and distribution of RBM45 along with a look into potential future research on this multifunctional RNA-binding protein.

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SummaryRNA recognition motif-type RNA-binding domain containing proteins (RBDPs) participate in RNA metabolism including regulating mRNA stability, nuclear-cytoplasmic shuttling, and splicing. Rbm45 is an RBDP first cloned from rat brain and expressed spatiotemporally during rat neural development. More recently, RBM45 has been associated with pathological aggregates in the human neurological disorders amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and Alzheimer's. Rbm45 and the neural developmental protein musashi-1 are in the same family of RDBPs and have similar expression patterns. In contrast to Musashi-1, which is upregulated during colorectal carcinogenesis, we found no association of RBM45 overexpression in human colon cancer tissue. In order to begin characterizing RNA-binding partners of Rbm45, we have successfully cloned and expressed peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/274647 doi: bioRxiv preprint first posted online Mar. 2, 2018; 2 human RBM45 in an Intein fusion-protein expression system. Furthermore, to gain a better understanding of the molecular genetics and evolution of Rbm45, we used an in silico approach to analyze the gene structure of the human and mouse Rbm45 homologues and explored the evolutionary conservation of Rbm45 in metazoans. Human RBM45 and mouse Rbm45 span ~17 kb and 13 kb, respectively, and contain 10 exons, one of which is non-coding. Both genes have TATA-less promoters with an initiator and a GC-rich element. Downstream of exon 10, both homologues have canonical polyadenylation signals and an embryonic cytoplasmic polyadenylation element. Moreover, our data indicate Rbm45 is conserved across all metazoan taxa from sponges (phylum Porifera) to humans (phylum Chordata), portending a fundamental role in metazoan development.