Introns

An intron is any nucleotide sequence within a gene that is removed by RNA splicing while the final mature RNA product of a gene is being generated. The term intron refers to both the DNA sequence within a gene and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final mature RNA after RNA splicing are exons. Introns are found in the genes of most organisms and many viruses, and can be located in a wide range of genes, including those that generate proteins, ribosomal RNA (rRNA), and transfer RNA (tRNA). When proteins are generated from intron-containing genes, RNA splicing takes place as part of the RNA processing pathway that follows transcription and precedes translation.  See Spliceosomes

The word intron is derived from the term intragenic region, i.e. a region inside a gene. Although introns are sometimes called intervening sequences, the term "intervening sequence" can refer to any of several families of internal nucleic acid sequences that are not present in the final gene product, including inteins, untranslated sequences (UTR), and nucleotides removed by RNA editing, in addition to introns.

Alternative splicing

Alternative splicing refers to the way that different combinations of exons can be joined together. This idea was first put forward by Walter Gilbert. He proposed that the different permutations of exons could produce different protein isoforms. These in turn would have different chemical and biological activities.

There are many forms of alternative splicing, all of which can result in different RNAs and hence proteins generated from the same gene.

There is exon skipping, where an exon can be missed completely, intron retention, where intronic sequence is included, mutually exclusive exons, where, for example, either exon 2 or exon 3 are included in the RNA, but not both, or alternative 5’ (5 prime) or 3’ donor sites can be used, resulting in part of an exon being missed out.

It is now thought that between 30 and 60% of human genes undergo alternative splicing. Moreover, it is said that many human diseases may be connected to problems with splicing. 

One example of a human gene that undergoes alternative splicing is fibronectin. Over 20 different isoforms of fibronectin have been discovered. These have all been produced from different combinations of fibronectin gene exons.

Possible Functions.:--  even after removal---After transcription of a eukaryotic pre-mRNA, its introns are removed by the spliceosome, joining exons for translation. The intron products of splicing have long been considered 'junk' and destined only for destruction. But because they are large in size and under weak selection constraints, many introns have been evolutionarily repurposed to serve roles after splicing. Some spliced introns are precursors for further processing of other encoded RNAs such as small nucleolar RNAs, microRNAs, and long noncoding RNAs.

Other intron products have long half-lives and can be exported to the cytoplasm, suggesting that they have roles in translation. Some viruses encode introns that accumulate after splicing and play important but mysterious roles in viral latency. Turnover of most lariat-introns is initiated by cleavage of their internal 2'-5' phosphodiester bonds by a unique debranching endonuclease, and the linear products are further degraded by exoribonucleases. However, several introns appear to evade this turnover pathway and the determinants of their stability are largely unknown. Whereas many stable intron products were discovered serendipitously, new experimental and computational tools will enable their direct identification and study. Finally, the origins and mechanisms of mobility of eukaryotic introns are mysterious, and mechanistic studies of the intron life cycle may yield new insights into how they arose and became widespread.

See "SA" opposite---"It is widely believed that introns are remnants of genetic sequences that once served as spacers between the stretches of DNA that coded for specific, comparatively simple proteins. During the evolution of complex proteins, regions of the genetic code (known as domains) may have been shuffled and brought together to generate new sequences that code for novel protein structures that took on new functions. This hypothesis is based on the observation that the relative positions of introns in genes remain largely the same in organisms as diverse as Drosophila melanogaster (the fruit fly), Caenorhabditis elegans (a widely studied nematode), mice and humans. Walter Gilbert of Harvard University has laid out many of the details of this hypothesis.

"In addition, some researchers have proposed that introns serve as a mechanism that selects for genes that will be expressed early (rather than late) during the development of an organism. This idea is not based on extensive experimentation, however, so its plausibility is uncertain."

"First, let's start with some classifications. There are at least five different types of introns. Some of them are ribozymes, RNA molecules that are catalytically active, meaning that they facilitate certain chemical reactions; some of these ribozymes are able to perform a reaction in which they splice themselves out of the original transcript. The most common type of intron is called a spliceosomal or nuclear intron; the name comes from the cellular machinery, known as the spliceosome, which is responsible for splicing and making sure that the genetic sequences in introns are not translated into junk proteins. This type of intron is the one found in the nuclear genes of humans.

In 1978 Walter Gilbert of Harvard expressed a different view of the nature of introns (in the same report in which he coined the terms 'exon' and 'intron'). He suggested that introns could speed up evolution by promoting genetic recombinations between exons. This process (which he called 'exon shuffling') would be directly associated with formation of new genes. Introns, from this perspective, have a profound purpose. They serve as hot spots for recombination in the formation of new combinations of exons. In other words, they are in our genes because they have been used during evolution as a faster pathway to assemble new genes.

Telomeres would be introns also.  <img src="/864219ee-c099-5c72-a98b-0af803e3b5a2.png"/>

Introns

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