Abstract
Micro RNAs (miRNAs) are ~22 nucleotide molecules that regulate gene expression post-transcriptionally and govern a wide range of physiological and developmental processes. Evidence now indicates that miRNAs can also coordinately down-regulate transcript levels for very large groups of genes in a tissue-specific manner, in addition to their ability to suppress protein translation. Here, we examine expression of specific miRNAs and Dicer ribonuclease that is required for miRNA biogenesis in mouse and rat lenses. Northern blot analysis demonstrated lens expression of brain-specific miR−124 and miR−7 in lenses, as well as miR−125b and let−7a. In addition, we provide evidence that muscle specific miR−1 is not present in lens. We detected Dicer transcripts in 21 day, 6 week, and 1 year mouse lenses and 15 day rat lens, and detected Dicer protein in adult lens protein samples. Immunohistochemical examination of late embryonic, post-natal, and adult rat lens sections identified expression of Dicer in differentiating fiber cells that undergo pronounced cell elongation in the lens interior and anterior epithelial cells. The present study provides evidence that miRNAs, which include brain-specific forms, and Dicer are expressed in mammalian lenses, indicating that fundamental aspects of miRNA biology are utilized by the lens during late embryonic and post-natal development and in adult lenses.
Similar content being viewed by others
References
Ambros V (2001) microRNAs: tiny regulators with great potential. Cell 107:823–826
Ambros V (2004a) The functions of animal microRNAs. Nature 431:350–355
Ambros V, Lee RC (2004b) Identification of microRNAs and other tiny noncoding RNAs by cDNA cloning. Methods Mol Biol 265:131–158
Andley UP, Patel HC, Xi JH, Bai F (2004) Identification of genes responsive to UV-A radiation in human lens epithelial cells using complementary DNA microarrays. Photochem Photobiol 80:61–71
Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297
Billy E, Brondani V, Zhang H, Muller U, Filipowicz W (2001) Specific interference with gene expression induced by long, double-stranded RNA in mouse embryonal teratocarcinoma cell lines. Proc Natl Acad Sci USA 98:14428–14433
Bloemendal H, Benedetti EL, Ramaekers FC, Dunia I, Kibbelaar MA, Vermorken AJ (1979) Is the cytoskeleton-plasma membrane complex involved in lens protein biosynthesis?. Mol Biol Rep 5:99–103
Doench JG, Petersen CP, Sharp PA (2003) siRNAs can function as miRNAs. Genes Dev 17:438–442
Faulkner-Jones B, Zandy AJ, Bassnett S (2003) RNA stability in terminally differentiating fibre cells of the ocular lens. Exp Eye Res 77:463–476
Frederikse PH, Ren XO (2002). Lens defects and age-related fiber cell degeneration in a mouse model of increased AbetaPP gene dosage in Down syndrome. Am J Pathol 161:1985–1990
Frederikse PH, Zigler JS Jr. (1998). Presenilin expression in the ocular lens. Curr Eye Res 17:947–952
Frederikse PH, Yun E, Kao HT, Zigler JS Jr., Sun Q, Qazi AS (2004) Synapsin and synaptic vesicle protein expression during embryonic and post-natal lens fiber cell differentiation. Mol Vis 10:794–804
Goswami S, Sheets NL, Zavadil J, Chauhan BK, Bottinger EP, Reddy VN, Kantorow M, Cvekl A (2003) Spectrum and range of oxidative stress responses of human lens epithelial cells to H2O2 insult. Invest Ophthalmol Vis Sci 44:2084–2093
Houbaviy HB, Murray MF, Sharp PA (2003) Embryonic stem cell-specific MicroRNAs. Dev Cell 5:351–358
Hutvagner G, McLachlan J, Pasquinelli AE, Balint E, Tuschl T, Zamore PD (2001) A cellular function for the RNA-interference enzyme Dicer in the maturation of the let−7 small temporal RNA. Science 293:834–838
Ivanov D, Dvoriantchikova G, Pestova A, Nathanson L, Shestopalov VI (2005) Microarray analysis of fiber cell maturation in the lens. FEBS Lett 579:1213–1219
Johnson SM, Grosshans H, Shingara J, Byrom M, Jarvis R, Cheng A, Labourier E, Reinert KL, Brown D, Slack FJ (2005) RAS is regulated by the let−7 microRNA family. Cell 120:635–647
Kim J, Krichevsky A, Grad Y, Hayes GD, Kosik KS, Church GM, Ruvkun G (2004) Identification of many microRNAs that copurify with polyribosomes in mammalian neurons. Proc Natl Acad Sci USA 101:360–365
Kolb FA, Zhang H, Jaronczyk K, Tahbaz N, Hobman TC, Filipowicz W (2005) Human dicer: purification, properties, and interaction with PAZ PIWI domain proteins. Meth Enzymol 392:316–336
Krek A, Grun D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, Macmenamin P, da Piedade I, Gunsalus KC, Stoffel M, Rajewsky N (2005) Nat Genet. Epub: April 3
Lagos-Quintana M, Rauhut R, Meyer J, Borkhardt A, Tuschl T (2003) New microRNAs from mouse and human. RNA 9:175–179
Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J, Lee J, Provost P, Radmark O, Kim S, Kim VN (2003) The nuclear RNase III Drosha initiates microRNA processing. Nature 425:415–419
Li G, Percontino L, Sun Q, Qazi AS, Frederikse PH (2003) Beta-amyloid secretases and beta-amloid degrading enzyme expression in lens. Mol Vis 9:179–183
Lim LP, Lau NC, Garrett-Engele P, Grimson A, Schelter JM, Castle J, Bartel DP, Linsley PS, Johnson JM (2005) Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 433:769–773
Ozaki L (1988) Newly synthesized proteins in a cell-free system supplemented with human and bovine membrane-bound polysomes isolated from lens fiber cells. Ophthalmic Res 20:363–367
Pasquinelli AE, Ruvkun G (2002) Control of developmental timing by micrornas and their targets. Annu Rev Cell Dev Biol 18:495–513
Pasquinelli AE, Reinhart BJ, Slack F, Martindale MQ, Kuroda MI, Maller B, Hayward DC, Ball EE, Degnan B, Muller P, Spring J, Srinivasan A, Fishman M, Finnerty J, Corbo J, Levine M, Leahy P, Davidson E, Ruvkun G (2000) Nature 408:86–89
Ramaekers FC, Selten-Versteegen AM, Benedetti EL, Dunia I, Bloemendal H (1980) In vitro synthesis of the major lens membrane protein. Proc Natl Acad Sci USA 77:725–729
Reneker LW, Xie L, Xu L, Govindarajan V, Overbeek PA (2004) Activated Ras induces lens epithelial cell hyperplasia but not premature differentiation. Int J Dev Biol 48:879–888
Robins H, Li Y, Padgett RW (2005) Incorporating structure to predict microRNA targets. Proc Natl Acad Sci USA 102:4006–4009
Ruotolo R, Grassi F, Percudani R, Rivetti C, Martorana D, Maraini G, Ottonello S (2003) Gene expression profiling in human age-related nuclear cataract. Mol Vis 9:538–548
Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V (2004) Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol 5:R13
Sioud M (2004) Therapeutic siRNAs. Trends Pharmacol Sci 25:22–28
Song E, Lee SK, Wang J, Ince N, Ouyang N, Min J, Chen J, Shankar P, Lieberman J (2003) RNA interference targeting Fas protects mice from fulminant hepatitis. Nat Med 9:347–351
Stark AJ, Brennecke J, Russell RB, Cohen SM (2003) Identification of Drosophila. MicroRNA targets. PLoS Biol 1(3):E60
Takamizawa J, Konishi H, Yanagisawa K, Tomida S, Osada H, Endoh H, Harano T, Yatabe Y, Nagino M, Nimura Y, Mitsudomi T, Takahashi T (2004) Reduced expression of the let−7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 64:3753–3756
Wen Y, Shi ST, Unakar NJ, Bekhor I (1991) Crystallin mRNA concentrations and distribution in lens of normal and galactosemic rats. Implications in development of sugar cataracts. Invest Ophthalmol Vis Sci 32:1638–1647
Xu P, Vernooy SY, Guo M, Hay BA (2003) The Drosophila microRNA Mir−14 suppresses cell death and is required for normal fat metabolism. Curr Biol 13:790–795
Zeng Y, Cullen BR (2005) Recognition and cleavage of primary microRNA precursors by the nuclear processing enzyme Drosha. EMBO J 24:138–148
Zeng Y, Yi R, Cullen BR (2003) MicroRNAs and small interfering RNAs can inhibit mRNA expression by similar mechanisms. Proc Natl Acad Sci USA 100:9779–9784
Acknowledgements
We thank Esther Yun and Yancy Van Patten for technical assistance during the course of this project. We thank W. Filipowicz (Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland) for antibodies and discussion and advice during this study. We also thank Debasish Sinha (John Hopkins, Baltimore MD) for providing histological sections and helpful discussion.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Frederikse, P.H., Donnelly, R. & Partyka, L.M. miRNA and Dicer in the mammalian lens: expression of brain-specific miRNAs in the lens. Histochem Cell Biol 126, 1–8 (2006). https://doi.org/10.1007/s00418-005-0139-0
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00418-005-0139-0