11.13
lncRNA - Long Non-coding RNAs
In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-cod…
Long non-coding RNAs or lncRNAs can regulate gene expression and other cellular processes. They are widespread and are found in plants, animals, bacteria, and viruses; however, they show low sequence conservation between different species.
LncRNAs are RNA transcripts longer than 200 nucleotides that are not translated into proteins; however, most are processed the same way as precursor mRNA through splicing and the addition of a 5’ cap and 3’ poly-A tail.
Compared to protein synthesis, RNA synthesis takes less energy and occurs more rapidly. As RNA is produced in the nucleus, it can be immediately used for gene regulation and can provide a faster response than proteins, which need to be imported from the cytoplasm.
LncRNA can perform their functions through several different mechanisms. When present near DNA, lncRNA can act as a scaffold for proteins by forming multiple stem-loop structures where proteins can bind and carry out their function, like chromatin-modifying proteins or transcriptional activators and repressors.
Like microRNA, lncRNA can act as guide RNA where its one part binds to various protein complexes whereas another part can selectively base pair with target DNA region and thereby helps in localization of the protein complexes.
LncRNA can act as alternative binding sites or sponges, sequestering some molecules away from their target location. For example, lncRNAs bind to microRNAs and prevent their interaction with their target mRNA.
LncRNA can base-pair with a complementary region in mRNA. This base-pairing can inhibit pre-mRNA splicing by hiding particular splice sites or can block the translation of mature mRNA.
Some lncRNA also carry exons and produce small peptides of unknown function.
LncRNAs are emerging as a significant player in additional cellular processes such as chromatin modifications and epigenetic regulation, as well as several diseases such as cancer and neurological diseases
View the full transcript and gain access to JoVE Core videos
Q1: What are long non-coding RNAs and how do they differ from other RNA types?
Long non-coding RNAs (lncRNAs) are RNA molecules longer than 200 nucleotides that do not encode proteins. Unlike messenger RNAs, which carry genetic instructions for protein synthesis, lncRNAs function as regulatory molecules. They play diverse roles in gene regulation, including chromatin modification and transcriptional control, making them critical components of cellular gene expression networks.
Q2: How do lncRNAs regulate gene expression at the molecular level?
lncRNAs regulate gene expression through multiple mechanisms, including interaction with chromatin-modifying complexes and recruitment of transcriptional machinery. They can act as scaffolds or guides to direct regulatory proteins to specific genomic locations. This positions lncRNAs as key players in regulation of expression occurs at multiple steps, influencing both transcriptional and post-transcriptional processes.
Q3: What is the relationship between lncRNAs and epigenetic regulation?
lncRNAs function as epigenetic regulators by recruiting histone-modifying enzymes and chromatin remodeling complexes to target genes. They can establish or maintain chromatin states that activate or silence gene expression without altering DNA sequences. This epigenetic role allows lncRNAs to create stable, heritable changes in gene accessibility and expression patterns across cell divisions.
Q4: How do lncRNAs compare to microRNAs in their regulatory functions?
While both lncRNAs and microRNAs regulate gene expression, they operate through distinct mechanisms. microRNAs typically bind to mRNA sequences to block translation or promote degradation, whereas lncRNAs often function as scaffolds or guides for protein complexes. lncRNAs generally have longer sequences and more complex three-dimensional structures, enabling broader regulatory capabilities than the smaller, sequence-specific microRNAs.
Q5: Can lncRNAs influence cell-specific gene expression patterns?
Yes, lncRNAs contribute significantly to cell-specific gene expression by directing tissue-specific transcriptional regulators to appropriate target genes. They can interact with co-activators and co-repressors to establish cell-type-specific chromatin landscapes. This allows different cell types to express distinct gene sets despite sharing identical genomes, supporting cellular differentiation and specialization.
Q6: What mechanisms allow lncRNAs to achieve specificity in their regulatory targets?
lncRNAs achieve target specificity through complementary base pairing with DNA or RNA sequences and through specific protein-binding domains. Their extended length and complex secondary structures enable recognition of multiple regulatory elements simultaneously. This combinatorial binding allows lncRNAs to distinguish between similar genomic regions and direct regulatory complexes with high precision to intended targets.
Q7: How do lncRNAs contribute to the overall control of gene expression in eukaryotic cells?
lncRNAs function as versatile regulators that integrate multiple cellular signals to control gene expression outcomes. They work alongside transcription regulators, activators and repressors to fine-tune chromatin accessibility and transcriptional activity. By coordinating with other regulatory molecules, lncRNAs enable cells to respond dynamically to developmental cues and environmental changes while maintaining stable cell identity.