Structure–function relationships in human ribonucleases: main distinctive features of the major RNase types

Sorrentino, Salvatore; Libonati, Massimo

doi:10.1016/s0014-5793(97)00086-0

Cited by 67 publications

(68 citation statements)

References 51 publications

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“…Shorter CGG repeat RNA was previously reported to form a G-tetraplex structure (11-13), as described earlier for DNA oligonucleotides of the same sequence (14,15). Comparison of both free energy values and melting temperatures (T m ) of (CCG) 20 , (CUG) 20 , (CAG) 20 , and (CGG) 20 in the presence of sodium and potassium salt demonstrated that none of these RNAs formed a tetraplex structure. However, the properties of (CGG) 20 differed slightly from those of other CNG repeat RNAs.…”

Section: Uan Repeats Form More Stable Structures Than Aun Repeats-supporting

confidence: 55%

“…However, the properties of (CGG) 20 differed slightly from those of other CNG repeat RNAs. In particular, a large decrease of free energy (⌬⌬G°3 7 ) equal to 2.36 kcal/mol was observed for (CGG) 20 melting in the presence of NaCl and KCl (Table 3). In the case of (CCG) 20 , (CUG) 20 , and (CAG) 20 , the changes in free energies were much smaller (0.18 -0.69 kcal/ mol).…”

Section: Uan Repeats Form More Stable Structures Than Aun Repeats-mentioning

confidence: 88%

“…(CGG) 20 Forms the Most Stable Hairpins, whereas (CCG) 20 Forms the Least Stable CNG Repeat Hairpins-The thermodynamic stabilities of four CNG trinucleotide repeat RNAs were obtained from UV-melting experiments at 260 nm ( Table 3). All of the investigated RNAs formed hairpins with similar architectures (5) and showed differences in stability, arising from the presence of different single-nucleotide N/N mismatches (10).…”

Section: Uan Repeats Form More Stable Structures Than Aun Repeats-mentioning

confidence: 99%

“…All of the investigated RNAs formed hairpins with similar architectures (5) and showed differences in stability, arising from the presence of different single-nucleotide N/N mismatches (10). The thermodynamic stabilities (⌬G°3 7 ) of (CCG) 20 , (CUG) 20 , (CAG) 20 , and (CGG) 20 in 100 mM NaCl were Ϫ6.68, Ϫ6.18, Ϫ4.57, and Ϫ2.57 kcal/mol, respectively. When the thermodynamic stability of the same RNAs was measured in 100 mM KCl, the free energies were Ϫ4.32, Ϫ6.00, Ϫ3.88, and Ϫ2.38 kcal/mol, respectively.…”

Section: Uan Repeats Form More Stable Structures Than Aun Repeats-mentioning

confidence: 99%

“…Comparison of both free energy values and melting temperatures (T m ) of (CCG) 20 , (CUG) 20 , (CAG) 20 , and (CGG) 20 in the presence of sodium and potassium salt demonstrated that none of these RNAs formed a tetraplex structure. However, the properties of (CGG) 20 differed slightly from those of other CNG repeat RNAs. In particular, a large decrease of free energy (⌬⌬G°3 7 ) equal to 2.36 kcal/mol was observed for (CGG) 20 melting in the presence of NaCl and KCl (Table 3).…”

Section: Uan Repeats Form More Stable Structures Than Aun Repeats-mentioning

confidence: 99%

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Structural Diversity of Triplet Repeat RNAs

Sobczak

Michlewski

Mezer

et al. 2010

Journal of Biological Chemistry

119

153

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Tandem repeats of various trinucleotide motifs are present in the human transcriptome, but the functions of these regular sequences, which likely depend on the structures they form, are still poorly understood. To gain new insight into the structural and functional properties of triplet repeats in RNA, we have performed a biochemical structural analysis of the complete set of triplet repeat transcripts, each composed of a single sequence repeated 17 times. We show that these transcripts fall into four structural classes. The repeated CAA, UUG, AAG, CUU, CCU, CCA, and UAA motifs did not form any higher order structure under any analyzed conditions. The CAU, CUA, UUA, AUG, and UAG repeats are ordered according to their increasing tendency to form semistable hairpins. The repeated CGA, CGU, and all CNG motifs form fairly stable hairpins, whereas AGG and UGG repeats fold into stable G-quadruplexes. The triplet repeats that formed the most stable structures were characterized further by biophysical methods. UV-monitored structure melting revealed that CGG and CCG repeats form, respectively, the most and least stable hairpins of all CNG repeats. Circular dichroism spectra showed that the AGG and UGG repeat quadruplexes are formed by parallel RNA strands. Furthermore, we demonstrated that the different susceptibility of various triplet repeat transcripts to serum nucleases can be explained by the sequence and structural features of the tested RNAs. The results of this study provide a comprehensive structural foundation for the functional analysis of triplet repeats in transcripts.Trinucleotide repeats (TNRs) 4 belong to a family of microsatellite sequences also known as short tandem repeats or simple sequence repeats. TNRs are present in both prokaryotic and eukaryotic genomes and, similar to other microsatellites, show high mutation rates resulting in frequent length variability. Polymorphic TNRs are better tolerated than dinucleotide and tetranucleotide repeats in translated sequences because their length variation does not change the open reading frame.A recent survey of the human genome reference sequence showed that it harbors more than 32,000 tracts of uninterrupted TNR sequences composed of six or more repeated units. In annotated human exons, which account for less than 3% of the genomic sequence, there are as many as 1,030 TNR tracts (61). Some AT-rich TNR types, such as CTT, AAC, and AAT, are particularly underrepresented in exons, whereas GC-rich repeats (CGG, CAG, and CCG) are highly overrepresented, implying that these sequences have a functional significance. The AT-rich and GC-rich TNRs tend to localize preferentially in the 3Ј-UTR and 5Ј-UTR, respectively (1). About 60% of exonic TNRs are localized in the open reading frame. These coding repeats are primarily translated to the poly-Gln, polyAla, poly-Glu, and poly-Leu tracts. However, the amino acid coding property of TNRs is not the only feature for which these sequences are selected in exons. The other properties of TNR sequences that manifest thems...

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Section: Uan Repeats Form More Stable Structures Than Aun Repeats-supporting

confidence: 55%

Section: Uan Repeats Form More Stable Structures Than Aun Repeats-mentioning

confidence: 88%

Section: Uan Repeats Form More Stable Structures Than Aun Repeats-mentioning

confidence: 99%

Section: Uan Repeats Form More Stable Structures Than Aun Repeats-mentioning

confidence: 99%

Section: Uan Repeats Form More Stable Structures Than Aun Repeats-mentioning

confidence: 99%

See 3 more Smart Citations

Structural Diversity of Triplet Repeat RNAs

Sobczak

Michlewski

Mezer

et al. 2010

Journal of Biological Chemistry

119

153

View full text Add to dashboard Cite

show abstract

Natural Catalytic Antibodies – Abzymes

Nevinsky

Buneva

2004

Catalytic Antibodies

112

760

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RNAStability: Chemistry, Measurement and Modulation

McDowall

2008

Wiley Encyclopedia of Chemical Biology

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Molecules composed of RNA perform many roles that are vital for the life and reproduction of all cellular organisms and viruses, one of which is the role of messengers that carry from genes the information required for the production of protein. A typical feature of messenger RNA (mRNA) is its relative instability, which ensures that the production of any particular protein soon comes to an end when it is no longer required and synthesis of the message is downregulated. Moreover, while a transcript is being produced, its rate of decay is as important as its rate of synthesis in determining its cellular concentration and thus, to a large extent, its level of function. The turnover of mRNA, and indeed all other types of RNA, is mediated by multiple ribonucleases. The activity of these enzymes in cells can be inhibited rapidly by chemical treatments; thus, for many experimental systems their presence does not pose a significant barrier to the study of gene regulation at the RNA level. However, the development of RNA‐based therapeutics such as small interfering RNAs and aptamers has required the introduction of modifications to prevent their degradation by ribonucleases within the cells and body fluids of humans. This article describes the properties of RNA that make it susceptible to ribonucleases and the techniques used to determine the stability of RNA molecules. It also provides examples of how RNA stability in livings cells is being modulated for biotechnology and clinical applications, and it reviews the strategies that are being adopted to increase the in vivo stability of RNAs with therapeutic potential.

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Structure–function relationships in human ribonucleases: main distinctive features of the major RNase types

Cited by 67 publications

References 51 publications

Structural Diversity of Triplet Repeat RNAs

Structural Diversity of Triplet Repeat RNAs

Natural Catalytic Antibodies – Abzymes

RNAStability: Chemistry, Measurement and Modulation

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