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Related Concept Videos

Nucleic Acid Structure01:25

Nucleic Acid Structure

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The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms  a 5′ to 3′ phosphodiester linkage.
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RNA Stability01:53

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Intact DNA strands can be found in fossils, while scientists sometimes struggle to keep RNA intact under laboratory conditions. The structural variations between RNA and DNA underlie the differences in their stability and longevity. Because DNA is double-stranded, it is inherently more stable. The single-stranded structure of RNA is less stable but also more flexible and can form weak internal bonds. Additionally, most RNAs in the cell are relatively short, while DNA can be up to 250 million...
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Nucleic acids are the most important macromolecules for the continuity of life. They carry the cell's genetic blueprint and carry instructions for its functioning.
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Bacterial RNA Polymerase00:43

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Unlike eukaryotes, bacteria use a single RNA Polymerase (RNAP) to transcribe all genes. The different subunits of bacterial RNAPhave distinct functions. The multisubunit structure of the bacterial RNAP helps the enzyme to maintain catalytic function, facilitate assembly, interact with DNA and RNA, and self-regulate its activity.
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Base complementarity between the three base pairs of mRNA codon and the tRNA anticodon is not a failsafe mechanism. Inaccuracies can range from a single mismatch to no correct base pairing at all. The free energy difference between the correct and nearly correct base pairs can be as small as 3 kcal/ mol. With complementarity being the only proofreading step, the estimated error frequency would be one wrong amino acid in every 100 amino acids incorporated. However, error frequencies observed in...
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Updated: Sep 17, 2025

Probing RNA Structure with Dimethyl Sulfate Mutational Profiling with Sequencing In Vitro and in Cells
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RiNALMo: general-purpose RNA language models can generalize well on structure prediction tasks.

Rafael Josip Penić1, Tin Vlašić2, Roland G Huber3

  • 1Faculty of Electrical Engineering and Computing, University of Zagreb, Zagreb, Croatia.

Nature Communications
|July 2, 2025
PubMed
Summary
This summary is machine-generated.

Researchers developed the largest RNA language model, RiNALMo, to decode RNA sequences. This advanced model extracts hidden knowledge and predicts RNA structures, outperforming existing methods on unseen RNA families.

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Area of Science:

  • Bioinformatics
  • Computational Biology
  • Molecular Biology

Background:

  • Ribonucleic acid (RNA) is emerging as a key target for small-molecule drugs, necessitating a deeper understanding of its structure and function.
  • Vast amounts of unlabeled RNA sequence data generated by sequencing technologies hold significant untapped potential for biological insights.
  • Existing deep learning methods struggle with generalizing RNA secondary structure predictions to novel RNA families.

Purpose of the Study:

  • To introduce the RiboNucleic Acid Language Model (RiNALMo), the largest RNA language model developed to date.
  • To leverage advances in protein language models for analyzing RNA sequences.
  • To extract implicit structural information and hidden knowledge from large RNA datasets.

Main Methods:

  • Pre-training RiNALMo, a 650M parameter model, on a dataset of 36 million non-coding RNA sequences from diverse databases.
  • Utilizing a transformer-based architecture, similar to successful protein language models.
  • Evaluating RiNALMo's performance on various downstream tasks, including secondary structure prediction.

Main Results:

  • RiNALMo achieved state-of-the-art performance across multiple RNA-related downstream tasks.
  • Demonstrated superior generalization capabilities compared to existing deep learning models, particularly for predicting secondary structures of unseen RNA families.
  • Successfully captured implicit structural information embedded within RNA sequences.

Conclusions:

  • RiNALMo represents a significant advancement in analyzing RNA sequences and understanding their functions.
  • The model's ability to generalize to new RNA families addresses a critical limitation in current deep learning approaches for RNA structure prediction.
  • RiNALMo unlocks the potential of large unlabeled RNA datasets for drug discovery and biological research.