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Related Concept Videos

Types of RNA01:23

Types of RNA

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Overview
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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Riboswitches01:56

Riboswitches

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Riboswitches are non-coding mRNA domains that regulate the transcription and translation of downstream genes without the help of proteins. Riboswitches bind directly to a metabolite and can form unique stem-loop or hairpin structures in response to the amount of the metabolite present. They have two distinct regions – a metabolite-binding aptamer and an expression platform.
The aptamer has high specificity for a particular metabolite which allows riboswitches to specifically regulate...
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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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Ribozymes02:47

Ribozymes

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The term ribozyme is used for RNA that can act as an enzyme. Ribozymes are mainly found in selected viruses, bacteria, plant organelles, and lower eukaryotes. Ribozymes were first discovered in 1982 when Tom Cech’s laboratory observed Group I introns acting as enzymes. This was shortly followed by the discovery of another ribozyme, Ribonulcease P, by Sid Altman’s laboratory. Both Cech and Altman received the Nobel Prize in chemistry in 1989 for their work on ribozymes.
Ribozymes can...
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Experimental RNAi02:15

Experimental RNAi

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RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
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Ribosome Profiling02:24

Ribosome Profiling

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Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
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RNAa: Mechanisms, therapeutic potential, and clinical progress.

Yukang Qian1, Cody Liu2, Xuhui Zeng1

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Molecular Therapy. Nucleic Acids
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RNA activation (RNAa) uses small activating RNAs (saRNAs) to upregulate gene expression, offering therapeutic potential for diseases like cancer and metabolic disorders. MicroRNAs also play a role in this gene activation process.

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Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Therapeutics

Background:

  • RNA activation (RNAa) is a gene regulatory mechanism involving small activating RNAs (saRNAs) and microRNAs (miRNAs).
  • Unlike RNA interference (RNAi) that silences genes, RNAa upregulates gene expression transcriptionally via the RNA-induced transcriptional activation (RITA) complex.
  • Endogenous microRNAs exhibit dual functionality, participating in RNAa (mi-RNAa) and influencing cellular processes and disease.

Purpose of the Study:

  • To review the mechanisms of RNA activation.
  • To highlight recent advancements in microRNA-mediated RNAa (mi-RNAa).
  • To discuss the therapeutic development of saRNAs.

Main Methods:

  • Literature review of RNA activation mechanisms.
  • Analysis of studies on saRNA and miRNA functions in gene regulation.
  • Examination of clinical advancements in RNAa-based therapeutics.

Main Results:

  • saRNAs can stably upregulate target gene expression at the transcriptional level.
  • Emerging evidence supports saRNAs as a therapeutic strategy for metabolic disorders, hearing loss, tumors, and Alzheimer's disease.
  • Clinical development includes saRNA drug candidates like MTL-CEBPA for hepatocellular carcinoma and RAG-01 for bladder cancer.

Conclusions:

  • RNAa represents a promising gene activation strategy with significant therapeutic implications.
  • Further research into mi-RNAa and saRNA development is crucial for advancing RNAa-based therapies.
  • The clinical success of saRNA candidates underscores the therapeutic potential of RNA activation.