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Translation
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
The Qβ RNA was translated successfully by cell-free extracts from wheat embryos (Davies and Kaesberg 1973). The three products were synthesized which co-electrophoresed with the Qβ proteins synthesized in the E. coli extracts, and the smallest one was clearly identified as coat protein. Furthermore, optimal conditions were selected for the efficient Qβ RNA translation, among other synthetic and natural messages, by the wheat germ protein-synthesizing system (Rychlik and Zagórski 1978). The Qβ RNA translation in wheat germ, as well as in the cell-free extracts of reticulocytes, contributed further strongly by the elucidation of the role of the messenger capping, namely, of the 5′-terminal 7-methylguanosine residue, in translation of mammalian mRNAs (Bergmann and Lodish 1979).
Analysis of Small RNA Species: Phylogenetic Trends
Published in S. K. Dutta, DNA Systematics, 2019
Mirko Beljanski, Liliane Le Goff
Eukaryotic cells contain, structually and functionally, small RNAs differing from other types of known cellular RNAs.105–107 In HeLa cells some of the small RNA (Sn RNAs) components are located mainly in the nucleoplasm and one mainly in the nucleoli.106 All USn RNAs: U1, U2, U3, U4, U5, and U6 exist in RNP particles. The analysis of several of these RNAs revealed the presence of a 5′ cap (a base m2,2,7-methylguanosine) that differs from the 5′ cap of mRNA (m7-G).77 This explains why Sn RNAs are not translated in the cytoplasm. Among Sn RNAs, U3 RNA is particularly localized in the nucleus and has not been found in any other site in the cell. It may play a role in transcription of the rRNA from the rDNA templates by maintaining stable open gene complexes.77 Detailed analysis of Sn RNAs has been described.80 The U RNAs contain a large number of more or less clustered uridine residues. U5 RNA is very enriched in uridine (35%). RNase T1 fingerprints of the purified U3 RNA, U2, and U1 are practically identical (# 300 nucleotides) in HeLa cells, human normal fibroblasts, and Novikoff hepatoma cells. These uridine rich low molecular weight RNAs appear to have been conserved throughout evolution.108
Hemoglobinopathies
Published in Victor A. Bernstam, Pocket Guide to GENE LEVEL DIAGNOSTICS in Clinical Practice, 2019
Variations in the clinical phenotype of β-thalassemia have been traced to mutations in the regulatory sequences outside the b-globin gene, which control the transcriptional efficiency of the b-globin genemutations affecting RNA processing: RNA modification at the cap (7-methylguanosine) siteRNA cleavagepolyadenylationsplicingmutations affecting translation of the mRNA into globin
The molecular structure and biological functions of RNA methylation, with special emphasis on the roles of RNA methylation in autoimmune diseases
Published in Critical Reviews in Clinical Laboratory Sciences, 2022
Wanwan Zhou, Xiao Wang, Jun Chang, Chenglong Cheng, Chenggui Miao
N1-methyladenosine (m1A), N6,2-O-dimethyladenosine (m6Am), and 7-methylguanosine (m7G) are newly discovered types of RNA methylation. The m1A modification is abundant in post-transcription transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs) in eukaryotes and affects the regulation of mRNA translation [21]. The m6Am modification is an evolutionarily conserved change that differs functionally from m6A, does not alter mRNA transcription or stability, but negatively affects the cap-dependent translation of methylated mRNAs [22]. The m7G modification regulates mRNA transcription, microRNA (miRNA) biosynthesis, biological functions, tRNA stability, 18S rRNA processing, and maturation [23]. The relationships between m1A, m6Am, and m7G modifications and autoimmune diseases have not been reported and their functions and mechanisms need to be explored.
Therapeutic Perspective of Temozolomide Resistance in Glioblastoma Treatment
Published in Cancer Investigation, 2021
Qin Xia, Liqun Liu, Yang Li, Pei Zhang, Da Han, Lei Dong
The standard treatment for GB patients includes tumor resection surgery followed by auxiliary fractionated radiotherapy and chemotherapy (5). Temozolomide (TMZ), the standard chemotherapeutic drug in GB treatment, is a DNA alkylating agent that can cross the blood-brain barrier (BBB) to exert its effects. TMZ exerts its cytotoxicity by transferring methyl groups to the N3 site on adenines [N3-methyladenine (N3-MeA), 9.2%] as well as the N7 and O6 sites on guanines [N7-methylguanosine (N7-MeG), >70%; O6-methylguanine (O6-MeG), <6%] (6), which leads to mismatched base pairs. Then, DNA mismatch repair will result in DNA strand breaks, which induce cell cycle arrest at G2/M that eventually leads to cell apoptosis (7,8). However, the addition of TMZ to the standard GB therapy only prolongs median survival by 2.5 months (9), the recurrence of GB implies the existence of TMZ-resistant tumor cells. Since GB cells rapidly invade adjacent brain structures, these motile GB cells that potentially evade treatment will lead to tumor recurrence after surgery, chemotherapy, and radiation therapy (10).
Gordon Dixon, protamines, and the atypical patterns of gene expression in spermatogenic cells
Published in Systems Biology in Reproductive Medicine, 2018
Findings that the cis-elements which repress Prm1 mRNA translation in round spermatids in transgenic mice are located in the 3ʹUTR was one of the first reports of a 3ʹUTR regulatory element in a eukaryotic cell (Braun et al. 1989b). Translation of a mouse mRNA encoding a cysteine-rich structural protein in sperm mitochondria (SMCP) is also primarily repressed by the 3ʹUTR (Hawthorne et al. 2006; Bagarova et al. 2010; Cullinane et al. 2015). Since translation initiates at the 5ʹ-ends of mRNAs, it was unexpected that translational regulation by 3ʹUTR cis-elements would turn out to be far more common than regulation by 5ʹUTR cis-elements (Jackson et al. 2010). The importance of the 3ʹUTR is explained by the closed-loop model in which proteins bound to the 5ʹ 7-methylguanosine cap and the 3ʹ poly(A) tail mRNA interact during translation (Jacobson 1996). The closed-loop model is a unifying principle of cytoplasmic regulation of gene expression in eukaryotic cells, and implicates interactions of the 5ʹ and 3ʹ ends of mRNAs in many mechanisms of post-transcriptional regulation. The enigmatic observation that poly(A) tails on translated trout, chicken and mouse protamine mRNAs are shorter than those on repressed mRNAs is consistent with a well-known phenomenon, translation-dependent poly(A) shortening, which ultimately leads to the degradation of defective or unneeded mRNAs (Chen and Shyu 2011; Kleene 2016).