Nucleic acids are essential for carrying genetic information and come in diverse conformations critical for their biological functions. From the well-known double helix of DNA to the unique folds of transfer RNA (tRNA) and microRNA (miRNA), the conformational diversity of nucleic acids plays a central role in various cellular processes. In this educational blog, we will delve into the intricacies of nucleic acid conformation, with a specific focus on DNA helices (A, B, Z), tRNA, and miRNA.
DNA Helices:
Our knowledge of genetics was completely transformed when Watson and Crick discovered the double helix structure of DNA. DNA can take on various helical conformations; the B-, A-, and Z-form helices being the most prevalent ones. DNA's conventional structure, known as the B-form helix, is a right-handed double helix that has about ten base pairs in each turn. The A-form helix is more compact than the B-form and has a broader major groove and a smaller minor groove. It is present in RNA-DNA hybrids and some DNA-RNA complexes. The left-handed Z-form helix has a zigzag backbone and is typically formed in areas with a high concentration of G-C base pairs or under high salt concentrations.
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| Attribution- File:Difference DNA RNA-DE.svg: Sponk / *translation: Sponk, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons |
tRNA (Transfer RNA):
During translation, tRNA molecules act as adapters between messenger RNA (mRNA) and amino acids, which is essential for the synthesis of proteins. The secondary structure of tRNA adopts a distinctive cloverleaf structure, and it has several kinds of conserved structural features that are essential for its function. On one end of the tRNA molecule is the amino acid attachment site, also known as the acceptor stem. On the other end is the anticodon loop, which has three nucleotides corresponding to the mRNA codon. Accurate amino acid recognition and transport to the growing polypeptide chain are made possible by a unique tertiary structure of tRNA, which includes the L-shaped fold formed by base pairing interactions.
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| Attribution: Yikrazuul, CC BY-SA 3.0 <https://creativecommons.org/licenses/by-sa/3.0>, via Wikimedia Commons |
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| Attribution: VWALevi2020, CC BY 4.0 <https://creativecommons.org/licenses/by/4.0>, via Wikimedia Commons |
microRNA (miRNA):
miRNAs are small, non-coding RNA molecules that bind to target mRNAs to either promote or inhibit translation, therefore regulating the expression of specific genes. Sequence-specific interactions between miRNAs and target mRNAs determine their characteristics, in unlike tRNA, which takes on a well-defined secondary and tertiary structure. To be processed by the RNA interference (RNAi) pathway, miRNAs must form secondary structures like hairpin loops. Various regulatory functions within gene expression networks are made possible by miRNAs' conformational flexibility.
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| Attribution: Kelvinsong, CC BY 3.0 <https://creativecommons.org/licenses/by/3.0>, via Wikimedia Commons |
Structural Insights and Functional Implications:
The biological roles of nucleic acids are closely linked with the many conformations that they take. Variations in helical structure affect DNA-protein interactions and gene regulation. DNA helices are essential for the storage and transmission of genetic information. Because of its unique structure, tRNA facilitates the fidelity of protein synthesis by accurately decoding mRNA sequences during translation. The specificity and efficacy of gene regulation are determined by miRNA conformational dynamics, wherein the structural features dictate target recognition and binding affinity.
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| Attribution: Mjeltsch, CC0, via Wikimedia Commons |
The study of nucleic acid conformation is a fascinating field that encompasses a broad spectrum of structural motifs and functional applications. The diverse conformations of nucleic acids underpin the complexity of cellular functions, from the well-known DNA double helix to the intricate folds of tRNA and miRNA. Researchers can gain significant insights into the mechanism of genetic information flow, gene expression regulation, and disease pathogenesis by deciphering the structural principles guiding nucleic acid conformation. The more complex aspects of nucleic acid structure we study, the more opportunities arise to understand and manipulate biological processes for therapeutic purposes.
