Alternative Splicing in Molecular Biology

A process where a single gene can produce multiple protein variants by combining different combinations of exons.

Exons that are always included in the final mRNA transcript, regardless of the splicing pattern.

Exons that can be included or excluded from the final mRNA transcript, depending on the specific splicing event.

A type of splicing where the mRNA is always processed in the same way, resulting in only one protein product.

Different versions of the same gene that arise from alternative splicing. Each isoform has a unique combination of exons.

A sequence within an intron that resembles a splice site but is not actually used for splicing. It can potentially interfere with splicing regulation.

The process by which a gene is transcribed into RNA, then spliced to remove introns and produce a mature mRNA transcript.

A protein responsible for recognizing and removing introns from pre-mRNA during splicing.

The process of removing introns from pre-mRNA to produce mature mRNA.

Non-coding sequences within a gene that are removed during splicing.

Coding sequences within a gene that are retained in the mature mRNA.

A protein component of the spliceosome that plays a crucial role in spliceosome assembly and function, specifically by maintaining the conformation of the active site and positioning the pre-mRNA.

A genetic disorder caused by mutations in the Prp8 gene, resulting in defects in the spliceosome and leading to degeneration of photoreceptors, causing blindness.

A process that allows for the production of multiple protein isoforms from a single gene by selectively including or excluding exons.

The regulatory sequences within pre-mRNA that influence the selection of splice sites during splicing.

Splicing codes are deciphered by RNA-binding proteins (RBPs) to determine which sequences in pre-mRNA are exons and introns.

Exons with strong splicing codes have a higher chance of being included in the final mRNA. They contain consensus sequences and binding sites for splicing enhancers, which attract RBPs.

Splicing activators, such as SR proteins, bind to exonic splicing enhancers (ESEs). They help recruit splicing machinery (U2AF and U1 snRNP) to the splice sites, making the splicing process more efficient.

Splicing repressors, such as hnRNP proteins, block splicing by binding to intronic splicing silencers (ISSs). This prevents the splicing machinery from assembling properly.

hnRNP proteins can also bind to ISSs flanking an exon, preventing other proteins from binding and causing the exon to be skipped during splicing.

Exon definition describes the process of identifying which sequences in pre-mRNA are exons, especially important in humans.

Intron definition involves the splicesosome directly assembling and recognizing the splicing sites within an intron.

Three factors contribute to alternative splicing (AS) regulation: Changes in RNA-binding protein expression, changes in upstream signaling pathways, and changes in the rate of transcription.

Cancer cells switch from using mitochondria for energy production to relying heavily on glycolysis, even in the presence of oxygen. This is called the Warburg effect, or anaerobic glycolysis.

Pyruvate kinase M (PKM) is an enzyme involved in glycolysis. Cancer cells often have a slower-acting version of the PKM enzyme, leading to build-up of glycolysis intermediates, which are then used for cancer cell growth.

Alternative splicing is a process where different versions of a protein can be produced from the same gene, depending on which parts of the gene are included in the final mRNA. PKM has two main isoforms, PKM1 and PKM2, created through alternative splicing.

RNA editing is a process that changes the sequence of RNA after it has been transcribed from DNA. It can alter the protein that's made from the RNA.

Adenosine Deaminases Acting on RNA (ADAR) are proteins that perform RNA editing. They convert adenosine (A) to inosine (I) in RNA, modifying the sequence.

RNA editing can affect a wide range of cellular processes, including neurotransmission, lipid metabolism, and potentially cancer.

RNA editing is a widespread mechanism, with about 85% of pre-mRNAs estimated to be edited in humans. This often happens in non-coding regions of RNA, like the 3' UTR (untranslated region).

Alu elements are short DNA sequences found in human DNA. They can be involved in RNA editing.

A type of RNA editing that converts adenosine (A) to inosine (I). Inosine then pairs with guanine (G) instead of uracil (U).

A type of RNA editing that converts cytidine (C) to uridine (U). Uridine then pairs with adenine (A) instead of guanine (G).

A disorder characterized by the formation of tumors on nerve tissue, including the brain, spinal cord, and nerves. It is caused by mutations in the NF1 gene.

A truncated form of the NF1 protein, lacking tumor suppressor functions. It is caused by a premature stop codon created by C-to-U editing.

A group of genetic disorders resulting in tumor formation in nerve tissue.

These mutations change the sequence of the RNA molecule, which can alter the splicing code. This can lead to disease because incorrect proteins are produced.

Point mutations are changes in a single nucleotide within a DNA sequence. They can affect RNA splicing by altering the signals that tell the splicing machinery where to cut and join the RNA. These changes can cause abnormal splicing patterns.

These sequences within genes tell the splicing machinery where to start and stop splicing. Mutations in these sites can change the splicing pattern, leading to aberrant protein production.

ESE and ESS influence the splicing process by promoting or suppressing the inclusion of a particular exon in the final mRNA. Mutations in these sequences can alter the balance between inclusion and exclusion, affecting the final protein product.

HGPS is a rare genetic disorder that causes premature aging. It is caused by a mutation in the LMNA gene, which encodes a protein called lamin A. The mutation creates a new 5' splice site, leading to the production of a shortened and abnormal version of lamin A.

The mutation in HGPS creates a new 5' splice site within exon 11 of the LMNA gene. This leads to the inclusion of a smaller portion of exon 11 in the final mRNA, resulting in a shortened and dysfunctional protein.

LMNA is a gene that produces a protein called lamin A, which is essential for nuclear structure and function. Mutations in this gene can lead to various disorders, including HGPS, muscular dystrophy, and other conditions.

LMNA is involved in nuclear structure and function. The protein produced by this gene (lamin A) acts like a scaffolding protein, supporting the nuclear membrane. Mutations in this gene alter the way the protein is made, impacting nuclear structure and function.