Hypothetical Double-Helical Poly(A) Formation in a Cell and Its Possible Biological Significance

Zarudnaya, M. I.; Hovorun, Dmytro М.

doi:10.1080/152165499306441

Cited by 9 publications

(9 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While the cell does not normally contain substantial concentrations of ammonium ions and is generally not acidic, protein mediation, acidic cellular compartments, metabolic conditions, or environmental acidic stress could possibly induce duplexed poly(rA) to form in living cells. As has been hypothesized ( 36 ), the formation of duplexed poly(rA) during the nuclear process of polyadenylation could limit poly(rA) lengthening, thereby regulating mRNA 3′ poly(rA) size, or increase mRNA half-life in the cytoplasm by protecting mRNAs from 3′-to-5′ deadenylases that degrade single-stranded poly(rA). The structure reported here may facilitate design of reagents able to detect parallel stranded poly(rA) helices in cells and elsewhere.…”

Section: Discussionmentioning

confidence: 90%

Crystal structure of a poly(rA) staggered zipper at acidic pH: evidence that adenine N1 protonation mediates parallel double helix formation

et al. 2016

View full text Add to dashboard Cite

We have solved at 1.07 Å resolution the X-ray crystal structure of a polyriboadenylic acid (poly(rA)) parallel and continuous double helix. Fifty-nine years ago, double helices of poly(rA) were first proposed to form at acidic pH. Here, we show that 7-mer oligo(rA), i.e. rA7, hybridizes and overlaps in all registers at pH 3.5 to form stacked double helices that span the crystal. Under these conditions, rA7 forms well-ordered crystals, whereas rA6 forms fragile crystalline-like structures, and rA5, rA8 and rA11 fail to crystallize. Our findings support studies from ∼50 years ago: one showed using spectroscopic methods that duplex formation at pH 4.5 largely starts with rA7 and begins to plateau with rA8; another proposed a so-called ‘staggered zipper’ model in which oligo(rA) strands overlap in multiple registers to extend the helical duplex. While never shown, protonation of adenines at position N1 has been hypothesized to be critical for helix formation. Bond angles in our structure suggest that N1 is protonated on the adenines of every other rAMP−rAMP helix base pair. Our data offer new insights into poly(rA) duplex formation that may be useful in developing a pH sensor.

show abstract

Section: Discussionmentioning

confidence: 90%

Crystal structure of a poly(rA) staggered zipper at acidic pH: evidence that adenine N1 protonation mediates parallel double helix formation

et al. 2016

View full text Add to dashboard Cite

show abstract

“…3 A role for long poly(A) tails in recruiting HuD to RNA is supported by in vitro decay analyses of GAP-43 mRNA, in which stabilization by HuD was dependent on poly(A) tails of at least 150 As (60). All observations made to date suggest that the contacts made between Hu proteins and long poly(A) tails are of a different nature than Hu/ARE contacts and are likely related to the ultrastructure of long poly(A)-tracts (27), which have been proposed to form double helices in vivo (61). Such higher order structures may present interaction sites for RRM3 and/or other parts of Hu proteins distinct from the conventional RNA-binding surface.…”

Section: Discussionmentioning

confidence: 97%

Characterization of the Interaction between Neuronal RNA-binding Protein HuD and AU-rich RNA

Park-Lee

Kim

Laird-Offringa

2003

Journal of Biological Chemistry

View full text Add to dashboard Cite

Hu proteins have been shown to bind to AU-rich elements (AREs) in the 3 -untranslated region of unstable mRNAs. They can thereby inhibit the decay of labile transcripts by antagonizing destabilizing proteins that target these AU-rich sequences. Here we examine the sequence preferences of HuD to elucidate its possible role in counteracting mRNA decay. Using repeats of the prototype destabilizing sequence UU(AUUU) n AUU, we show that all three HuD RNA-binding domains participate in binding to AU-tracts that can be as short as 13 residues, depending on the position of the remaining As. Removal of the A residues, resulting in a poly(U)-tract, increased the affinity of HuD for RNA, suggesting that the presence of As in destabilizing elements might favor the recruitment of other proteins and/or prevent HuD from binding too tightly to AREs. In vitro selection experiments with randomized RNAs confirmed the preference of HuD for poly(U). RNA binding analysis of the related protein HuB showed a similar preference for poly(U). In contrast, tristetraprolin, an mRNA destabilizing protein, strongly prefers AU-rich RNA. Many labile mRNAs contain U-tracts in or near their AREs. Individual AREs may thus differentially affect mRNA halflife by recruiting a unique complement of stabilizing and destabilizing factors.

show abstract

“…New drugs developed must be able to specifically bind to unique structural organizations in RNA to regulate the gene expression. Virtually all mRNAs in eukaryotic cells have a poly(A) tail at the 3 end that is an important determinant in the maturation and stability of mRNA [10][11][12] and also the initiation of translation. Post translational polyadenylation of mRNA is catalyzed by the enzyme poly(A) polymerase.…”

Section: Introductionmentioning

confidence: 99%

Molecular aspects on the specific interaction of cytotoxic plant alkaloid palmatine to poly(A)

Giri

Hossain

Kumar

2006

International Journal of Biological Macromolecules

View full text Add to dashboard Cite

Hypothetical Double-Helical Poly(A) Formation in a Cell and Its Possible Biological Significance

Cited by 9 publications

References 22 publications

Crystal structure of a poly(rA) staggered zipper at acidic pH: evidence that adenine N1 protonation mediates parallel double helix formation

Crystal structure of a poly(rA) staggered zipper at acidic pH: evidence that adenine N1 protonation mediates parallel double helix formation

Characterization of the Interaction between Neuronal RNA-binding Protein HuD and AU-rich RNA

Molecular aspects on the specific interaction of cytotoxic plant alkaloid palmatine to poly(A)

Contact Info

Product

Resources

About