What are long non-coding RNAs (lncRNAs), and what roles do they play in gene regulation?
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Mastering this deck will deepen your understanding of cutting-edge molecular mechanisms, enabling you to interpret complex genetic regulation and contribute to research or diagnostics in genetic diseases and gene therapy. You'll gain insights into non-coding RNA functions, gene silencing strategies, and molecular pathology, enhancing your ability to innovate in genomics and personalized medicine.
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| 1 | What are long non-coding RNAs (lncRNAs), and what roles do they play in gene regulation? |
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Explore emerging areas like non-coding RNAs, gene silencing, and the molecular basis of genetic diseases.
Long non-coding RNAs (lncRNAs) are RNA molecules longer than 200 nucleotides that do not encode proteins. They regulate gene expression through various mechanisms such as chromatin remodeling, transcriptional interference, and acting as molecular scaffolds or decoys for proteins and microRNAs, thereby influencing processes like X-chromosome inactivation and cell differentiation. |
| Think of lncRNAs as regulatory RNA architects shaping gene activity. |
| 2 | How does RNA interference (RNAi) mediate gene silencing? | RNA interference (RNAi) involves small interfering RNAs (siRNAs) or microRNAs (miRNAs) binding to complementary mRNA sequences, leading to mRNA degradation or translational repression. This process effectively silences specific gene expression post-transcriptionally. | RNAi acts like a molecular off-switch for targeted genes. |
| 3 | What is the molecular basis of Fragile X syndrome? | Fragile X syndrome results from a CGG trinucleotide repeat expansion in the FMR1 gene's 5' untranslated region, leading to hypermethylation and gene silencing. The loss of FMRP protein causes abnormal synaptic development and intellectual disability. | Think of repeat expansions as genetic 'glitches' that turn off critical genes. |
| 4 | Describe the role of DNA methylation in gene silencing. | DNA methylation involves the addition of methyl groups to cytosine bases, primarily in CpG islands, leading to chromatin condensation and reduced accessibility of transcriptional machinery. This epigenetic modification can stably silence gene expression without altering the DNA sequence. | Methylation is like adding a 'do not disturb' sign to genes. |
| 5 | What are microRNAs (miRNAs), and how do they regulate gene expression? | MicroRNAs (miRNAs) are small (~22 nucleotides) non-coding RNAs that bind to complementary sequences in target mRNAs, typically in the 3' UTR, leading to translational repression or mRNA degradation. They are crucial for fine-tuning gene expression during development and cellular responses. | miRNAs act as molecular dimmers, adjusting gene output finely. |
| 6 | How can non-coding RNAs contribute to the development of cancer? | Dysregulation of non-coding RNAs like lncRNAs and miRNAs can lead to abnormal gene expression, promoting oncogene activation or tumor suppressor silencing. For example, certain miRNAs can inhibit tumor suppressor genes, while some lncRNAs can facilitate metastasis. | Non-coding RNAs can be both guards and villains in cancer biology. |
| 7 | Explain the concept of epigenetic inheritance related to molecular mechanisms. | Epigenetic inheritance refers to heritable changes in gene expression that do not involve alterations in the DNA sequence, primarily maintained through DNA methylation, histone modifications, and non-coding RNAs during cell division. These mechanisms can be influenced by environmental factors. | Think of epigenetics as a heritable 'software' that controls genetic 'hardware'. |
| 8 | What is RNA-mediated gene silencing and give an example? | RNA-mediated gene silencing involves small RNAs like siRNAs or miRNAs that direct the degradation or translational repression of target mRNAs, exemplified by the use of siRNA in experimental knockdown of specific genes to study their functions. | RNA silencing is like sending molecular 'kill commands' to specific mRNAs. |
| 9 | Describe how CRISPR interference (CRISPRi) can be used for gene silencing. | CRISPRi employs a catalytically inactive Cas9 (dCas9) fused to a repressor domain, guided by sgRNA to specific gene promoters, blocking transcription initiation without cutting DNA, effectively silencing gene expression. | CRISPRi is like a molecular roadblock preventing gene transcription. |
| 10 | What is the significance of non-coding RNAs in human diseases? | Non-coding RNAs are involved in regulating gene expression networks; their dysregulation is associated with diseases such as cancer, neurodegenerative disorders, and cardiovascular diseases. For example, miRNAs can function as oncogenes or tumor suppressors. | Non-coding RNAs are critical regulatory molecules whose imbalance can lead to disease. |
| 11 | What techniques are used to study non-coding RNAs in the laboratory? | Techniques include RNA sequencing (RNA-seq) for expression profiling, Northern blotting, qRT-PCR for quantification, in situ hybridization for localization, and functional assays like knockdown or overexpression experiments. | Multiple molecular tools help decode the roles of non-coding RNAs. |
| 12 | How do histone modifications influence gene silencing in epigenetics? | Histone modifications such as methylation or deacetylation lead to chromatin condensation, making DNA less accessible to transcription machinery, thus contributing to gene silencing. | Histone marks act as epigenetic 'flags' signaling gene activity states. |
| 13 | Describe the concept of RNA editing and its impact on gene regulation. | RNA editing involves enzymatic modifications of RNA nucleotides after transcription, such as adenosine-to-inosine editing, which can alter codons or splicing sites, impacting protein diversity and gene regulation. | RNA editing is like editing a script after it's written to change its message. |
| 14 | What is the role of piwi-interacting RNAs (piRNAs) in the genome? | piRNAs are small non-coding RNAs that primarily silence transposable elements in germ cells, protecting genome integrity during gametogenesis. | piRNAs act as genome guardians in reproductive cells. |
| 15 | How can epigenetic drugs influence gene silencing mechanisms? | Epigenetic drugs such as DNA methyltransferase inhibitors or histone deacetylase inhibitors can reverse abnormal gene silencing, reactivating tumor suppressor genes or correcting dysregulated gene expression in diseases. | Epigenetic drugs 'unlock' silenced genes therapeutically. |
| 16 | Explain the concept of allele-specific expression in the context of epigenetics. | Allele-specific expression occurs when one allele of a gene is expressed preferentially over the other, often regulated by epigenetic marks such as DNA methylation or histone modifications, contributing to phenomena like genomic imprinting. | It's like one copy of a gene being 'turned on' while the other is 'off' due to epigenetic marks. |
| 17 | What are the potential therapeutic applications of understanding non-coding RNAs? | Therapeutic applications include designing miRNA mimics or inhibitors, targeting lncRNAs involved in disease pathways, and developing RNA-based drugs for gene regulation, offering personalized treatment options for genetic and complex diseases. | Non-coding RNAs are promising targets for next-generation therapeutics. |