Musashi-1, an RNA-binding protein, is indispensable for survival of photoreceptors.
Musashi-1 (Msi1), an RNA-binding protein (RBP), has been postulated to play important roles in the maintenance of the stem-cell state, differentiation, and tumorigenesis. However, the expression and function of Msi1 in differentiated cells remain obscure. Here we show that Msi1 is expressed in mature photoreceptors and retinal pigment epithelium (RPE) cells, and is indispensable for the survival of photoreceptors. We found in the adult newt eye that Msi1 is expressed in all photoreceptors and RPE cells as well as in the retinal stem/progenitor cells in the ciliary marginal zone (CMZ). We found in the analyses of the newt normal and regenerating retinas that the expression profiles of the Msi1 transcripts and protein isoforms in the photoreceptors are different from those in the retinal stem/progenitor cells. Furthermore, we found that all photoreceptors and RPE cells of the adult mice also express Msi1, and that Msi1 knockout (Msi1-KO) results in degeneration of photoreceptors and a lack of a visual cycle protein RPE65 in the microvilli of RPE cells. Taken together, our current results demonstrate that the expression of Msi1 in mature photoreceptors and RPE cells is evolutionarily conserved, and that Msi1 bears essential functions for vision. Considering such an Msi1-KO phenotype in the retina, it is now reasonable to address whether defects of the Msi1 functions are responsible for inherited retinal diseases. Studying the regulation of Msi1 and the target RNAs of Msi1 in photoreceptors and RPE cells might contribute to fundamental and clinical studies of retinal degeneration.
Susaki
Kanako
K
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Kaneko
Jun
J
Yamano
Yuka
Y
Nakamura
Kenta
K
Inami
Wataru
W
Yoshikawa
Taro
T
Ozawa
Yoko
Y
Shibata
Shinsuke
S
Matsuzaki
Osamu
O
Okano
Hideyuki
H
Chiba
Chikafumi
C
D000595:Amino Acid Sequence; D029845:Amphibian Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D005136:Eye Proteins / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020419:Photoreceptor Cells, Vertebrate / Q000166:cytology* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism; D012455:Salamandridae; D013234:Stem Cells / Q000378:metabolism; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase
D029845:Amphibian Proteins; D002352:Carrier Proteins; D005136:Eye Proteins; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D019745:cis-trans-Isomerases; D000099178:Retinoid Isomerohydrolase; C104786:Msi1h protein, mouse