Genomic analyses of musashi1 downstream targets show a strong association with cancer-related processes.
Musashi1 (Msi1) is a highly conserved RNA-binding protein with pivotal functions in stem cell maintenance, nervous system development, and tumorigenesis. Despite its importance, only three direct mRNA targets have been characterized so far: m-numb, CDKN1A, and c-mos. Msi1 has been shown to affect their translation by binding to short elements located in the 3'-untranslated region. To better understand Msi1 functions, we initially performed an RIP-Chip analysis in HEK293T cells; this method consists of isolation of specific RNA-protein complexes followed by identification of the RNA component via microarrays. A group of 64 mRNAs was found to be enriched in the Msi1-associated population compared with controls. These genes belong to two main functional categories pertinent to tumorigenesis: 1) cell cycle, cell proliferation, cell differentiation, and apoptosis and 2) protein modification (including ubiquitination and ubiquitin cycle). To corroborate our findings, we examined the impact of Msi1 expression on both mRNA (transcriptomic) and protein (proteomic) expression levels. Genes whose mRNA levels were affected by Msi1 expression have a Gene Ontology distribution similar to RIP-Chip results, reinforcing Msi1 participation in cancer-related processes. The proteomics study revealed that Msi1 can have either positive or negative effects on gene expression of its direct targets. In summary, our results indicate that Msi1 affects a network of genes and could function as a master regulator during development and tumor formation.
de Sousa Abreu
Raquel
R
Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, Department of Cellular and Structural Biology, San Antonio, TX 78229-390, USA.
Sanchez-Diaz
Patricia C
PC
Vogel
Christine
C
Burns
Suzanne C
SC
Ko
Daijin
D
Burton
Tarea L
TL
Vo
Dat T
DT
Chennasamudaram
Soudhamini
S
Le
Shu-Yun
SY
Shapiro
Bruce A
BA
Penalva
Luiz O F
LO
D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D040901:Proteomics / Q000379:methods; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics
D020413:3' Untranslated Regions; C491297:MSI1 protein, human; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins