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Related Concept Videos

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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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.
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Types of RNA01:23

Types of RNA

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Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
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RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

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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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Transfer RNA Synthesis02:36

Transfer RNA Synthesis

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One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
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Detection of RNA-binding Proteins by In Vitro RNA Pull-down in Adipocyte Culture
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Long Non-Coding RNA Expression Levels Modulate Cell-Type-Specific Splicing Patterns by Altering Their Interaction

Felipe Wendt Porto1, Swapna Vidhur Daulatabad1, Sarath Chandra Janga2,3,4

  • 1Department of BioHealth Informatics, School of Informatics and Computing, IUPUI, Indianapolis, IN 46202, USA.

Genes
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Summary

Long non-coding RNAs (lncRNAs) significantly impact alternative splicing and gene regulation in a cell-type-specific manner. This study reveals lncRNAs can act as sponges, altering RNA-binding protein networks and cellular functions in diseases.

Keywords:
RNA-binding proteinsalternative splicingcancercell-type-specificfunctional enrichmentlong non-coding RNAprotein binding lncRNA spongessecondary RNA structure

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Area of Science:

  • Molecular Biology
  • Genomics
  • Epigenetics

Background:

  • Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cellular processes and disease.
  • Their precise contribution to post-transcriptional regulation, particularly alternative splicing, remains incompletely understood.
  • Understanding lncRNA-mediated gene regulation is crucial for developing novel therapeutic strategies for diseases like cancer.

Purpose of the Study:

  • To investigate the role of lncRNAs in modulating alternative splicing.
  • To analyze the impact of lncRNAs on downstream protein-RNA interaction networks.
  • To determine the cell-type specificity of lncRNA-driven alternative splicing and its functional consequences.

Main Methods:

  • Comparative analysis of RNA-sequencing data from lncRNA knockdown and wildtype samples across three human cell lines (HeLa, K562, U87).
  • High-confidence identification of alternative splicing events (skipped exons, retained introns) using a false discovery rate (fdr) < 0.01.
  • Analysis of RNA-binding protein (RBP) interaction profiles to identify cell-type-specific binding preferences at spliced regions.

Main Results:

  • Identification of 11,630 skipped exon and 5,895 retained intron events, impacting 759 genes at the post-transcriptional level upon lncRNA knockdown.
  • Observed significant cell-type specificity in both alternatively spliced genes and their associated cellular functions across different lncRNA knockdown experiments.
  • Demonstrated association between alternative splicing events and cell-type-specific RBP binding at intron-exon junctions, despite limited RBP binding data.

Conclusions:

  • lncRNAs play a critical role in regulating alternative splicing in a cell-type-specific manner.
  • lncRNAs can function as sponges, sequestering RBPs and thereby disrupting downstream cellular functions.
  • This lncRNA-mediated rewiring of protein-RNA interactions offers a potential mechanism for cell-type-specific gene dysregulation in disease contexts.