Shetty Sunil, Varshney Umesh
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560012, India.
Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, 560012, India; Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore, 560064, India
Proc Natl Acad Sci U S A. 2016 Oct 11;113(41):E6126-E6134. doi: 10.1073/pnas.1609550113. Epub 2016 Oct 3.
Ribosome biogenesis, a complex multistep process, results in correct folding of rRNAs, incorporation of >50 ribosomal proteins, and their maturation. Deficiencies in ribosome biogenesis may result in varied faults in translation of mRNAs causing cellular toxicities and ribosomopathies in higher organisms. How cells ensure quality control in ribosome biogenesis for the fidelity of its complex function remains unclear. Using Escherichia coli, we show that initiator tRNA (i-tRNA), specifically the evolutionarily conserved three consecutive GC base pairs in its anticodon stem, play a crucial role in ribosome maturation. Deficiencies in cellular contents of i-tRNA confer cold sensitivity and result in accumulation of ribosomes with immature 3' and 5' ends of the 16S rRNA. Overexpression of i-tRNA in various strains rescues biogenesis defects. Participation of i-tRNA in the first round of initiation complex formation licenses the final steps of ribosome maturation by signaling RNases to trim the terminal extensions of immature 16S rRNA.
核糖体生物合成是一个复杂的多步骤过程，其结果是rRNA的正确折叠、50多种核糖体蛋白的掺入及其成熟。核糖体生物合成的缺陷可能导致mRNA翻译过程中出现各种故障，从而在高等生物中引起细胞毒性和核糖体病。细胞如何确保核糖体生物合成的质量控制以保证其复杂功能的保真度仍不清楚。我们利用大肠杆菌表明，起始tRNA（i-tRNA），特别是其反密码子茎中进化上保守的三个连续GC碱基对，在核糖体成熟中起关键作用。i-tRNA细胞含量的缺陷会导致冷敏感性，并导致16S rRNA 3'和5'末端不成熟的核糖体积累。在各种菌株中过表达i-tRNA可挽救生物合成缺陷。i-tRNA参与第一轮起始复合物的形成，通过向核糖核酸酶发出信号以修剪未成熟16S rRNA的末端延伸，从而许可核糖体成熟的最后步骤。
