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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.
Different Types of RNA Have the Same Basic Structure
There are three main types of ribonucleic acid (RNA) involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). All three...
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RNA Splicing01:32

RNA Splicing

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Splicing is the process by which eukaryotic RNA is edited before its translation into protein. The RNA strand transcribed from eukaryotic DNA is called the primary transcript. The primary transcripts that become mRNAs are called precursor messenger RNAs (pre-mRNAs). Eukaryotic pre-mRNA contains alternating sequences of exons and introns. Exons are nucleotide sequences that code for proteins, whereas introns are the non-coding regions. In RNA splicing, introns are removed and exons are bonded...
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Eukaryotic RNA Polymerases00:58

Eukaryotic RNA Polymerases

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RNA Polymerase (RNAP) is conserved in all animals, with bacterial, archaeal, and eukaryotic RNAPs sharing significant sequence, structural, and functional similarities. Among the three eukaryotic RNAPs, RNA Polymerase II is most similar to bacterial RNAP in terms of both structural organization and folding topologies of the enzyme subunits. However, these similarities are not reflected in their mechanism of action.
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RNA Polymerase II Accessory Proteins02:36

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Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
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Alternative RNA Splicing02:18

Alternative RNA Splicing

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Alternative RNA splicing is the regulated splicing of exons and introns to produce different mature mRNAs from a single pre-mRNA. Unlike in constitutive splicing where a single gene produces a single type of mRNA, alternative splicing allows an organism to produce multiple proteins from a single gene and plays an important role in protein diversity.
There are five types of alternative RNA splicing that vary in the ways the pre-mRNA segments are removed or retained in the mature mRNA. The first...
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Leaky Scanning02:28

Leaky Scanning

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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
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LocARNA 2.0: Versatile Simultaneous Alignment and Folding of RNAs.

Sebastian Will1

  • 1LIX, CNRS UMR 7161, École Polytechnique, Institut Polytechnique de Paris, Palaiseau, France. sebastian.will@polytechnique.edu.

Methods in Molecular Biology (Clifton, N.J.)
|May 23, 2024
PubMed
Summary

Accurate RNA sequence alignment is crucial for understanding function. LocARNA 2.0 software offers fast, versatile simultaneous alignment and folding (SA&F) for large-scale RNA analysis, improving upon previous versions.

Keywords:
Comparative analysisMultiple sequence alignmentRNA alignmentRNA secondary structure predictionSimultaneous alignment and folding

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Area of Science:

  • Computational Biology
  • Bioinformatics
  • Molecular Biology

Background:

  • Accurate alignment of non-coding RNA sequences is essential for deciphering RNA function.
  • Inferring sequence homology and RNA structure is challenging, especially for sequences with low similarity, requiring simultaneous alignment and folding (SA&F).
  • SA&F is the gold standard for comparative RNA analysis but is computationally intensive.

Purpose of the Study:

  • Introduce LocARNA 2.0, a software package for versatile, fast, and accurate multiple RNA analysis.
  • Highlight the practical applications and performance improvements of LocARNA 2.0.
  • Demonstrate how LocARNA 2.0 makes advanced SA&F algorithms routinely applicable for large-scale studies.

Main Methods:

  • Implementation of a lightweight flavor of SA&F algorithms optimized for large-scale applications.
  • Combination of ensemble-based sparsification of the structure space and probabilistic banding strategies for enhanced performance.
  • Inclusion of tools for global and local RNA comparison, clustering, and multiple alignment using SA&F variants.

Main Results:

  • LocARNA 2.0 provides a versatile, fast, and accurate platform for analyzing multiple RNA sequences.
  • Ensemble-based sparsification and probabilistic banding significantly improve computational performance and ease of use.
  • The software enables flexible integration of prior knowledge through anchor and structure constraints.

Conclusions:

  • LocARNA 2.0 significantly advances large-scale comparative RNA analysis by providing efficient SA&F capabilities.
  • The software's performance enhancements and flexible features make it a valuable tool for RNA research.
  • LocARNA 2.0 facilitates deeper understanding of RNA function through improved sequence alignment and structural analysis.