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Related Concept Videos

RNA Structure01:19

RNA Structure

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The basic structure of RNA consists of a string of ribonucleotides attached by phosphodiester bonds. Although most RNA is single-stranded, it can form complex secondary and tertiary structures. Such structures play essential roles in the regulation of transcription and translation.
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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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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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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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Types of RNA01:23

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RNA polymerase (RNAP) carries out DNA-dependent RNA synthesis in both bacteria and eukaryotes. Bacteria do not have a membrane-bound nucleus. So, transcription and translation occur simultaneously, on the same DNA template.
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Orthrus: Towards Evolutionary and Functional RNA Foundation Models.

Philip Fradkin1,2, Ruian Shi1,2,3, Keren Isaev3

  • 1Vector Institute, Ontario, Canada.

Biorxiv : the Preprint Server for Biology
|October 17, 2024
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Summary
This summary is machine-generated.

Orthrus, a new Mamba-based foundation model, improves prediction of mature RNA properties by using biological data for training. This advance enhances understanding of RNA function and regulation from genomic data.

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Area of Science:

  • Genomics
  • Bioinformatics
  • Computational Biology

Background:

  • Predicting mature RNA properties from genomic data is challenging.
  • Existing foundation models lack biological domain knowledge.
  • Need for RNA-specific foundation models.

Purpose of the Study:

  • Introduce Orthrus, a Mamba-based foundation model for mature RNA.
  • Develop a novel self-supervised contrastive learning objective with biological augmentations.
  • Improve prediction of RNA properties and functions.

Main Methods:

  • Orthrus uses a self-supervised contrastive learning objective.
  • Trained on splice isoforms from 10 model organisms.
  • Utilizes orthologous genes from the Zoonomia Project (400+ mammalian species).

Main Results:

  • Orthrus learns latent representations clustering RNA by function and evolution.
  • Outperforms existing models on five mRNA property prediction tasks.
  • Requires less fine-tuning data than other models.

Conclusions:

  • Orthrus effectively captures mature RNA isoform representations.
  • Demonstrates capability in predicting divergent biological functions of transcript isoforms.
  • Advances RNA property prediction and functional analysis.