The molecular structure of polyadenylic acid

Rich, Alexander; Davies, David R.; Crick, Francis; Watson, James D.

doi:10.1016/s0022-2836(61)80009-0

Cited by 481 publications

(221 citation statements)

References 16 publications

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“…Two of these sites discussed above are the a and 0 regions in the D loop. Another region of variability is the fourth base pair in the D stem (positions [13][14][15][16][17][18][19][20][21][22] and the interactions associated with the nucleotide in position 9 with a base in the D stem. The fact that the major stabilizing interaction in the molecule is the extensive system of stacked purines and pyrimidines suggests to us that this feature of the structure is maintained in those molecules in which the pattern of hydrogen bonding differs somewhat from that found in the yeast tRNAPhe.…”

Section: Discussionmentioning

confidence: 99%

“…A possible pairing for this arrangement is shown in Fig 4c where In the eukaryotic initiator tRNAfmet, the sequence (T54, 4V55) becomes (A54, U55) while position 60 has an A instead of a pyrimidine. From studying the conformation of the TIC loop, it is likely that A can be inserted in position 54 in such a way that it could form a pair of hydrogen bonds with A58 using the hydrogen bonding found in helical polyadenylic aicd (14), whereas position 60 could accommodate an adenine instead of a pyrimidine. All the hydrogen bonded interactions and the base stacking system described for Class D4V5 are assumed to be applicable for the remaining tRNA classes with the exceptions noted below.…”

Section: Structural Features Of Yeast Phenylalanine Trnamentioning

confidence: 99%

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The General Structure of Transfer RNA Molecules

Kim

Sussman

Suddath

et al. 1974

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

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278

179

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The three-dimensional structure of yeast phenylalanine tRNA serves as a useful basis for understanding the tertiary structure of all tRNAs. A large number of tRNA sequences have been surveyed and some general conclusions are drawn. There are only a few regions in the molecule in which there are differences in the number of nucleotides; and the structure of yeast phenylalanine tRNA can accommodate these differences by forming or enlarging protuberances on the surface of the basic framework molecule. The nature and distribution of the differences in number of nucleotides are surveyed and possible hydrogen bonding interactions are discussed for a number of tRNA classes. The two most significant features of the molecule are the large number of stacking interactions which are seen to include most of the nucleotides in the molecule and the system of specifie hydrogen bonding interactions. It is likely that these stabilizing elements are preserved in all tRNA structures.Until recently the most striking feature of transfer RNA (tRNA) sequences has been the fact that they could all be arranged in the familiar cloverleaf diagram with complementary hydrogen bonding between the bases in the stem regions (1). In addition, some positions are always occupied by constant nucleotides. Almost 2 years ago, the x-ray diffraction analysis of yeast phenylalanine tRNA (tRNAPhe) at 4-A resolution showed that this molecule not only contains the double helical stems implicit in the cloverleaf diagram, but also was found to have an L shape with the anticodon loop at one end of the L, the acceptor stem at the other end, and the dihydrouracil (D) and TVC loops forming the corner of the molecule (2). More recently the x-ray diffraction analysis of this molecule has been extended to 3-resolution for both the orthorhombic (3, 4) and monoclinic crystal forms (5) and the tertiary interactions in both crystal forms appear very similar.The most striking feature of the 3-A analysis is the extent to which a large number of the bases which are constant to all tRNAs are used in the tertiary hydrogen bonding interactions.These, together with -base stacking, maintain the threedimensional form of the molecule. This suggests rather directly that the three-dimensional structure seen in yeast tRNAPhe may be generalized to understand the structure of all tRNAs. The idea that all tRNAs have a common or similar structure is not surprising in view of the fact that all tRNAs involved in protein synthesis must go through the ribosomal machinery. Here we discuss the manner in which the three-dimensional structure of yeast tRNAPhe may serve as a framework for understanding the structure of all tRNA molecules. We do this by comparing tRNA sequences (6) and suggesting plausible ways in which structural components in this molecule may be modified to fit in other tRNA sequences. Structural features of yeast phenylalanine tRNAThe preliminary details of yeast tRNAPhe tertiary interactions have been published (4, 5). Further improvement of the phases using a "part...

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Section: Discussionmentioning

confidence: 99%

Section: Structural Features Of Yeast Phenylalanine Trnamentioning

confidence: 99%

The General Structure of Transfer RNA Molecules

Kim

Sussman

Suddath

et al. 1974

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

Self Cite

278

179

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“…Under highly acidic conditions (pH 3), poly(A) strands (both in their RNA and DNA forms) have been reported to self--associate into parallel homoduplexes as a result of protonation of the adenine units 36,37,43,44 . We ascertained that CA--mediated assembly of d(A 15 ) under the conditions described above (pH 4.5) is distinct from the pH--driven poly(A) duplex, based on major differences between the CD spectra of these species.…”

Section: Evidence Of Ca--mediated Assembly Of D(a) 15mentioning

confidence: 99%

“…In the presence of poly(thymine), poly(adenine) can form double and triple helices. On its own, poly(adenine) can form a parallel homoduplex in acidic conditions, 36,37 whereas an antiparallel homoduplex can be formed at neutral pH with the addition of small molecule intercalators such as coralyne 30,31 . In principle, we can reprogram poly(adenine) interactions to induce assembly of a higher--order structure if we combine adenine with a small symmetric molecule such as cyanuric acid, that contains three complementary thymine--like faces (Fig.…”

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confidence: 99%

Reprogramming the assembly of unmodified DNA with a small molecule

et al. 2016

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The information storage and encoding ability of DNA arise from a remarkably simple 4--letter -A, T, G, C nucleobase code. Expanding this DNA 'alphabet' provides information about its function and evolution, and introduces new functionalities into nucleic acids and organisms. Previous efforts relied on the synthetically demanding incorporation of non--canonical bases into nucleosides. Here we report the discovery that a small molecule, cyanuric acid, with three thymine--like faces reprograms the assembly of unmodified poly(adenine) into stable, long and abundant fibers with a unique internal structure. Poly(A) DNA, RNA and PNA all form these assemblies. Our studies are consistent with the association of adenine and cyanuric acid units into a hexameric rosette, bringing together poly(A) triplexes with subsequent cooperative polymerization. Fundamentally, this study shows that small hydrogen--bonding molecules can be used to induce the assembly of nucleic acids in water, leading to new structures from inexpensive and readily available materials.

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“…Poly(A) will also complex with itself, forming hydrogen (43)(44)(45). Adenine-adenine pairing does exist, however, in naturally occurring RNA at neutral pH and at physiological ionic strength.…”

Section: Processing Mechanismsmentioning

confidence: 99%

Could poly(A) align the splicing sites of messenger RNA precursors?

Bina¹,

Feldmann²,

Deeley³

1980

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

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In general, poly(A)mRNA appears to be derived from larger nuclear RNA precursors. The maturation of these precursors involves excision of sequences of variable length from within the molecule and splicing of the remaining structural and coding sequences. The mechanism by which this process occurs is not known. It does not appear to operate solely through the recognition of a defined primary sequence or through the formation of a consistent secondary structure. We propose an alternative model in which poly(A) facilitates the splicing event by promoting the formation of triple-stranded structures within the mRNA precursor.The structural genes of eukaryotes and viruses that specify polyadenylated § mRNA species are interrupted by nucleotide sequences not represented in the mature mRNA transcripts. Such sequences have been termed "intervening sequences" or "introns" (for review see refs. 1-3). The primary products of such transcription units are large mRNA precursors that include intervening sequences (4, 5). Present evidence indicates that, after the addition of a poly(A) tract to its 3' end, the mRNA precursor is processed within the nucleus or during transport to the cytoplasm to produce a mature mRNA molecule (5-8). Processing is accomplished by the successive excision of introns and splicing of conserved sequences. The only examples of eukaryotic mRNAs that are known not to follow such a processing pathway are those specifying histones. Those histone genes that have been examined do not contain intervening sequences (9), and histone mRNAs are predominantly not polyadenylated (10)(11)(12) The conservation of sequences spanning the splicing sites in RNA species from evolutionarily distant organisms points both to a common general mechanism for processing of polyadenylated RNA and to the possibility that, in a given organism, processing may be catalyzed by a single enzyme or enzyme complex. At the moment, a mechanism that allows the accurate removal of intervening sequences from a mRNA precursor and the precise ligation of the remaining structural sequences is unknown. It seems likely that if the order of structural sequences is to be conserved, the ends of an intervening sequence must be brought close to each other prior to endonucleolytic cleavage, so that ligation can take place without physical separation of the 3' and 5' ends of the structural sequences that are to be spliced. However, intervening sequences are variable in length and, with the exception of the border regions already mentioned, possess no marked homologies or symmetries of sequence. Attempts to draw the ends of an intervening sequence together by maximizing Watson-Crick base pairing do not generate structures in which donor and acceptor sites exhibit a reasonably constant configuration. A splicing mechanism based solely on the maintenance of a fixed secondary structure also seems unlikely for other reasons. For example, it has been shown that intervening sequences are free to change much more rapidly than structural sequences (16)(17)(...

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The molecular structure of polyadenylic acid

Cited by 481 publications

References 16 publications

The General Structure of Transfer RNA Molecules

The General Structure of Transfer RNA Molecules

Reprogramming the assembly of unmodified DNA with a small molecule

Could poly(A) align the splicing sites of messenger RNA precursors?

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