Lack of secondary structure characterizes the 5′ ends of mammalian mitochondrial mRNAs

Jones, Christie N.; Wilkinson, Kevin A.; Hung, Kimberly T.; Weeks, Kevin M.; Spremulli, Linda L.

doi:10.1261/rna.909208

Cited by 56 publications

(52 citation statements)

References 26 publications

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“…In humans, this codon constitutes 20% of mRNA initiator methionines and 80% of internal methionines (15,16 by increasing the motional dynamics of the loop residues (17). A further study detailing the codon-binding characteristics and solution structure of hmASL Met f5CAU agreed with the f 5 C-dependent increase in residue dynamics (18).…”

mentioning

confidence: 60%

Expanded use of sense codons is regulated by modified cytidines in tRNA

Cantara

Murphy

DeMi̇rci̇

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Codon use among the three domains of life is not confined to the universal genetic code. With only 22 tRNA genes in mammalian mitochondria, exceptions from the universal code are necessary for proper translation. A particularly interesting deviation is the decoding of the isoleucine AUA codon as methionine by the one mitochondrial-encoded tRNA Met . This tRNA decodes AUA and AUG in both the A-and P-sites of the metazoan mitochondrial ribosome. Enrichment of posttranscriptional modifications is a commonly appropriated mechanism for modulating decoding rules, enabling some tRNA functions while restraining others. In this case, a modification of cytidine, 5-formylcytidine (f

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mentioning

confidence: 60%

Expanded use of sense codons is regulated by modified cytidines in tRNA

Cantara

Murphy

DeMi̇rci̇

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Since 29-O-adduct formation involves loss of this proton, the trend in pK a values offer a partial explanation for differing intrinsic reactivities. In some RNAs, a subset of cytidine residues, drawn as single-stranded, have low SHAPE reactivities Jones et al 2008). Given that the intrinsic reactivity of this nucleotide is, at most, only twofold different from the other nucleotides, we postulate that these cytidines may participate in a locally constraining interaction that remains to be fully characterized.…”

Section: Discussionmentioning

confidence: 93%

“…First, cytidine residues in flexible regions sometimes have lower SHAPE reactivities than other nucleotides with similar apparent local structures Jones et al 2008). Second, the pK a of the ribose 29-hydroxyl group varies by as much as 0.5 units as a function of the nucleobase in RNA mono-and dinucleotides (Jarvinen et al 1991;Velikyan et al 2001;Acharya et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Influence of nucleotide identity on ribose 2′-hydroxyl reactivity in RNA

Wilkinson¹,

Vasa²,

Deigan³

et al. 2009

RNA

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Hydroxyl-selective electrophiles, including N-methylisatoic anhydride (NMIA) and 1-methyl-7-nitroisatoic anhydride (1M7), are broadly useful for RNA structure analysis because they react preferentially with the ribose 29-OH group at conformationally unconstrained or flexible nucleotides. Each nucleotide in an RNA has the potential to form an adduct with these reagents to yield a comprehensive, nucleotide-resolution, view of RNA structure. However, it is possible that factors other than local structure modulate reactivity. To evaluate the influence of base identity on the intrinsic reactivity of each nucleotide, we analyze NMIA and 1M7 reactivity using four distinct RNAs, under both native and denaturing conditions. We show that guanosine and adenosine residues have identical intrinsic 29-hydroxyl reactivities at pH 8.0 and are 1.4 and 1.7 times more reactive than uridine and cytidine, respectively. These subtle, but statistically significant, differences do not impact the ability of selective 29-hydroxyl acylation analyzed by primer extension-based (SHAPE) methods to establish an RNA secondary structure or monitor RNA folding in solution because base-specific influences are much smaller than the reactivity differences between paired and unpaired nucleotides.

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“…They are synthesized by the mitochondrial translational machinery from nine monocistronic mRNAs and two dicistronic mRNAs with overlapping reading frames. Mitochondrial mRNAs contain few or no noncoding nucleotides prior to the 5Ј-terminal start codon and are largely unstructured at their 5Ј-ends (2,3). The exact number of nucleotides prior to the 5Ј-start codon in mature mitochondrial mRNAs has been determined in both humans and fruit flies.…”

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confidence: 99%

Preferential Selection of the 5′-Terminal Start Codon on Leaderless mRNAs by Mammalian Mitochondrial Ribosomes

Christian

Spremulli

2010

Journal of Biological Chemistry

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Mammalian mitochondrial mRNAs are basically leaderless, having few or no untranslated nucleotides prior to the 5-start codon. We demonstrate here that mammalian mitochondrial 55 S ribosomes preferentially form initiation complexes at a 5-terminal AUG codon over an internal AUG. The preferential use of the 5-start codon is also seen on mitochondrial 28 S small subunits, which suggests that mitochondrial translation initiation on leaderless mRNAs does not require the large ribosomal subunit. The selection of the 5-AUG is dependent on the presence of fMet-tRNA and is enhanced by the presence of the mitochondrial initiation factor IF2 mt . In prokaryotes, IF3 is believed to antagonize initiation on leaderless mRNAs. However, IF3 mt stimulates initiation complex formation on leaderless mRNAs when tested with 55 S ribosomes. The addition of even a few nucleotides 5 to the AUG codon significantly reduces the efficiency of initiation, highlighting the importance of the leaderless or nearly leaderless nature of mitochondrial mRNAs. In addition, very few initiation complexes could form on a hybrid mRNA construct consisting of tRNA Met attached at the 5-end of a mitochondrial protein-coding sequence. This observation demonstrates that post-transcriptional processing must occur prior to translation in mammalian mitochondria.In contrast to other genomes, the mammalian mitochondrial genome is very compact, containing ϳ16 kilobase pairs of DNA with very few noncoding nucleotides. This DNA encodes 2 rRNAs, 13 proteins, and 22 tRNAs (1). The 13 proteins are all essential components of the electron transport chain and ATP synthase. They are synthesized by the mitochondrial translational machinery from nine monocistronic mRNAs and two dicistronic mRNAs with overlapping reading frames. Mitochondrial mRNAs contain few or no noncoding nucleotides prior to the 5Ј-terminal start codon and are largely unstructured at their 5Ј-ends (2, 3). The exact number of nucleotides prior to the 5Ј-start codon in mature mitochondrial mRNAs has been determined in both humans and fruit flies. Direct analysis of the 5Ј-ends of the 11 open reading frames located at the 5Ј-ends of the human mitochondrial mRNAs demonstrated that post-transcriptional processing completely eliminates the 5Ј-leader in all but three mRNAs (4). These three mRNAs have one, two, and three nucleotides 5Ј to the start codon. None of the 5Ј-cistrons of Drosophila melanogaster mitochondrial mRNAs begin with noncoding nucleotides (5).Translation of mitochondrial mRNAs is accomplished by mitochondrial ribosomes, which sediment as 55 S particles and dissociate into 28 S and 39 S subunits. The translation process in mitochondria occurs with the help of two initiation factors: IF2 mt promotes the binding of fMet-tRNA to the 28 S small ribosomal subunit, and IF3 mt stimulates initiation complex formation by facilitating the dissociation of mitochondrial 55 S ribosomes. No factor homologous to prokaryotic IF1 has been found in mitochondria, and the role of this factor is thought to be carr...

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Lack of secondary structure characterizes the 5′ ends of mammalian mitochondrial mRNAs

Cited by 56 publications

References 26 publications

Expanded use of sense codons is regulated by modified cytidines in tRNA

Expanded use of sense codons is regulated by modified cytidines in tRNA

Influence of nucleotide identity on ribose 2′-hydroxyl reactivity in RNA

Preferential Selection of the 5′-Terminal Start Codon on Leaderless mRNAs by Mammalian Mitochondrial Ribosomes

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