膳食鐵營養狀況對於大鼠肌肉硫醇鹼基修飾tRNA的表現與其修飾作用之影響

• Main Authors: Hsu Yun-Hsin, 徐韻欣
• Other Authors: 劉奕方
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/89710967447750637755

碩士 === 輔仁大學 === 營養科學系 === 99 === Transfer RNA (tRNA) modifications play an important role in decoding of mRNA to ribosome. It is known that a lot of modified nucleosides in wobble position, especially modification in uridine. tRNALys, tRNAGlu, tRNAGln are modified to 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U), and is required for the proper decoding of NNR codons in eukaryotes. In yeast, IscS/Nfs1p is required for the post-transcriptional modification of thiouridine in tRNAs, however, the mechanism of 2-thiouridine modification is still unknown in mammals. The IscS protein (homologous to Nfs1p) is a cysteine desulfurase mainly in mitochondria, and supply sulfur atom to iron-sulfur protein biogenesis. Our previously study has demonstrated that mitochondrial IscS protein level was specifically decreased in iron-deficient skeletal muscle. In this study, we investigate the effect of dietary iron intake on the expression and thio-modification of 2-thiouridine tRNA, and the relationship between the mitochondrial IscS protein and thio-modification of thiouridine-containing tRNAs in skeletal muscle. Male weanling Wistar rats were divided to feed iron deficient diet (ID), paired-fed (IPF), and freely fed normal diet (AI). After 6 weeks, the hematological indices of iron status (hemoglobin, serum iron, transferrin saturation) in ID rats decreased to 60%, 80% and 89%, but the total iron binding capacity increased to 1.8 folds of AI rats. These indicate ID rats have severe iron-deficiency anemia. The expression of IscS protein in mitochondria of ID rats’ muscle reduced to 74%, and the level of tRNALys and tRNAGlu in muscle of ID rats decreased to 40% and 39% of AI rats, respectively. The level of thio-modification of tRNALys and tRNAGlu in muscle of ID rats also decreased to 24% and 58% of AI rats, respectively. In addition, the expression of tRNAGlu in muscle of IPF rats declined to 53% of AI rats. However, the thio-modification of tRNAGlu and tRNALys level and it thio-modification were not affected. In conclusion, our study demonstrate the expression of thiouridine-containing tRNA and its thio-modification, and mitochondrial IscS protein are modulated by iron deficiency in rat skeletal muscle. These results suggest that IscS may be involved in thio-modification of thiouridine-containing tRNAs in skeletal muscle.