A new unique form of microRNA from human heart, microRNA-499c, promotes myofibril formation and rescues cardiac development in mutant axolotl embryos

Journal of Biomedical Science

Larry F Lemanski¹  Michael C Hanna¹  Jessica Meyer¹  William Lian¹  Ashley Moses¹  Andrei Kochegarov¹ 

[1] Department of Biological and Environmental Sciences, Texas A&M University-Commerce, P.O. Box 3011, Commerce, TX 75429-3011, USA

关键词: microRNA;    Human embryonic heart RNA;    Cardiac mutant axolotl;    Tropomyosin;    Myofibrillogenesis;   

Others  :  824115
DOI  :  10.1186/1423-0127-20-20

 received in 2012-12-03, accepted in 2013-03-18,  发布年份 2013

【 摘 要 】

Background

A recessive mutation “c” in the Mexican axolotl, Ambystoma mexicanum, results in the failure of normal heart development. In homozygous recessive embryos, the hearts do not have organized myofibrils and fail to beat. In our previous studies, we identified a noncoding Myofibril-Inducing RNA (MIR) from axolotls which promotes myofibril formation and rescues heart development.

Results

We randomly cloned RNAs from fetal human heart. RNA from clone #291 promoted myofibril formation and induced heart development of mutant axolotls in organ culture. This RNA induced expression of cardiac markers in mutant hearts: tropomyosin, troponin and α-syntrophin. This cloned RNA matches in partial sequence alignment to human microRNA-499a and b, although it differs in length. We have concluded that this cloned RNA is unique in its length, but is still related to the microRNA-499 family. We have named this unique RNA, microRNA-499c. Thus, we will refer to this RNA derived from clone #291 as microRNA-499c throughout the rest of the paper.

Conclusions

This new form, microRNA-499c, plays an important role in cardiac development.

【 授权许可】

   
2013 Kochegarov et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

【 参考文献 】

• [1]Zhang C, Jia P, Huang X, Sferrazza GF, Athauda G, Achary MP, Wang J, Lemanski SL, Dube DK, Lemanski LF: Myofibril-inducing RNA (MIR) is essential for tropomyosin expression and myofibrillogenesis in axolotl hearts. J Biomed Sci 2009, 16:81. BioMed Central Full Text
• [2]Zhang C, Dube DK, Huang X, Zajdel RW, Bhatia R, Foster D, Lemanski SL, Lemanski LF: A point mutation in bioactive RNA results in the failure of mutant heart correction in Mexican axolotls. Anat Embryol 2003, 206:495-506.
• [3]Rueda-de-León E, Kochegarov A, Lian W, Athauda G, Zhang C, Maier J, Huang X, Achary MP, Moses A, Meyer J, Arms JD, Burlbaw SR, Lemanski SL, Lemanski LF: Human Heart RNA Promotes Tropomyosin Synthesis and Myofibrillogenesis in Mutant Axolotl Hearts. MD-Med Data 2011, 3:223-227.
• [4]Wilson KD, Hu S, Venkatasubrahmanyam S, Fu JD, Sun N, Abilez OJ, Baugh JJ, Jia F, Ghosh Z, Li RA, Butte AJ, Wu JC: Dynamic microRNA expression programs during cardiac differentiation of human embryonic stem cells: role for miR-499. Circ Cardiovasc Genet 2010, 3:426-435.
• [5]Hosoda T, Zheng H, Cabral-da-Silva M, Sanada F, Ide-Iwata N, Ogórek B, Ferreira-Martins J, Arranto C, D’Amario D, del Monte F, Urbanek K, D’Alessandro DA, Michler RE, Anversa P, Rota M, Kajstura J, Leri A: Human cardiac stem cell differentiation is regulated by a mircrine mechanism. Circ 2011, 123:1287-1296.
• [6]Bordzilovskaya NP, Dettlaff TA, Duhon ST, Malacinski GM: Developmental-stage series of axolotl embryos. In Developmental Biology of the Axolotl. Edited by Armstrong JB, Malacinski GM. New York: Oxford University Press; 1989:201-219.
• [7]Lemanski LF, Nakatsugawa M, Bhatia R, Erginel-Unaltuna N, Spinner BJ, Dube DK: A specific synthetic RNA promotes cardiac myofibrillogenesis in the Mexican axolotl. Biochem Biophys Res Com 1996, 229:974-981.
• [8]Mirbase, micro RNA database. http://www.mirbase.org webcite
• [9]Lemanski LF: Role of tropomyosin in actin filament formation in embryonic salamander heart cells. J Cell Biol 1979, 82:227-238.
• [10]Sluijter JP, van Mil A, van Vliet P, Metz CH, Liu J, Doevendans PA, Goumans MJ: MicroRNA-1 and -499 regulate differentiation and proliferation in human-derived cardiomyocyte progenitor cells. Arterioscler Thromb Vasc Biol 2010, 4:859-868.
• [11]Fu JD, Rushing SN, Lieu DK, Chan CW, Kong CW, Geng L, Wilson KD, Chiamvimonvat N, Bohele KR, Wu JC, Keller G, Hajjar RJ, Li RA: Distinct roles of microRNA-1 and -499 in ventricular specification and functional maturation of human embryonic stem cell-derived cardiomyocytes. PLoS One 2011, 6:e27417.
• [12]Jacobson AG, Duncan JT: Heart induction in salamanders. J Exp Zool 1968, 167:79-103.
• [13]Fullilove SL: Heart inductor: distribution of active factors in newt endoderm. J Exp Zool 1970, 75:323-326.