Diagram of the location of introns and exons within a gene.

Introns are sections of DNA that will be spliced out after transcription, but before the RNA is used. Introns are common in eukaryotic RNAs of all types, but are found in prokaryotic tRNA and rRNA genes only. The regions of a gene that remain in spliced mRNA are called exons. The number and length of introns varies widely among species and among genes within the same species. For example, the pufferfish Takifugu rubripes has little intronic DNA. Genes in mammals and flowering plants, on the other hand, often have numerous introns, which can be much longer than the nearby exons.

Introduction

Simple illustration of pre-mRNA to mRNA splicing.

Introns sometimes allow for alternative splicing of a gene, so that several different proteins that share some sections in common can be produced from a single gene. The control of mRNA splicing, and hence of which alternative is produced, is performed by a wide variety of signal molecules. Introns also sometimes contain "old code," sections of a gene that were probably once translated into protein but which are now discarded.

While it is widely believed that most of the sequence in any given intron is junk DNA with no known function, several short sequences that are important for efficient splicing are known. The exact mechanism for these intronic splicing enhancers is not well understood, but it is thought that they serve as binding sites on the transcript for proteins that stabilize the spliceosome. It is also possible that RNA secondary structure formed by intronic sequences may have an effect on splicing.

The discovery of introns led to the Nobel Prize in Physiology or Medicine in 1993 for Phillip Allen Sharp and Richard J. Roberts.

Some introns such as Group I and Group II introns are actually ribozymes that are capable of catalyzing their own splicing out of the primary RNA transcript. This self splicing was discovered by Thomas Cech who shared the 1989 Nobel Prize in Chemistry with Sidney Altman for the discovery of the catalytic properties of RNA.

Classification of Introns

Four classes of introns are known to exist:

• Nuclear Introns / Spliceosomal Introns
  

  Spliceosomal introns often reside in eukaryotic protein-coding genes. Within the intron, a 3' splice site, 5' splice site, and branch site are required for splicing. Splicing is catalyzed by the spliceosome which is a large RNA-protein complex composed of five small nuclear ribonucleoproteins (snRNPs, pronounced "snurps"). The RNA components of snRNPs interact with the intron and may be involved in catalysis. Two types of spliceosomes have been identified (the major and minor) which contain different snRNPs.

  • Major

  The major spliceosome splices introns containing GU at the 5' splice site and AG at the 3' splice site. It is composed of the U1, U2, U4, U5, and U6 snRNPs.

  U1- binds 5' splice site U2- binds the branch U4- inhibits U6, lost to activate spliceosome U5 - binds U1 and U2 to create lariat U6 - When, activated, displaces U1 and binds U2. U2-U6 forms active catalytic complex

  • Minor

  The minor spliceosome is very similar to the major spliceosome, however it splices rare introns with different splice site sequences. Here, the 3' and 5' splice sites are AU and AC, respectively. While the minor and major spliceosomes contain the same U5 snRNP, the minor spliceosome has different, but functionally analogous snRNPs for U1, U2, U4, and U6, which are respectively called U11, U12, U4atac, and U6atac. ^[1]

  • Trans-splicing

  Trans-splicing is a form of splicing that joins two exons that are not within the same RNA transcript.

  
  
• Group I intron
• Group II intron
• Group III intron

Sometimes group III introns are also identified as group II introns, because of their similarity in structure and function.

Nuclear or spliceosomal introns are spliced by the spliceosome and a series of snRNAs (small nuclear RNAs). There are certain splice signals (or consensus sequences) which abet the splicing (or identification) of these introns by the spliceosome.

Group I, II and III introns are self splicing introns and are relatively rare compared to spliceosomal introns. Group II and III introns are similar and have a conserved secondary structure. The lariat pathway is used in their splicing. They perform functions similar to the spliceosome and may be evolutionarily related to it. Group I introns are the only class of introns whose splicing requires a free guanine nucleoside. They possess a secondary structure different from that of group II and III introns. They are found in most bacteria and protozoa.

Intron evolution

There are two competing theories attempting to explain the origin and evolution of spliceosomal introns (Other classes of introns such as self-splicing and tRNA introns are not subject to much debate). These are popularly called as the Introns-Early (IE) or the Introns-Late (IL) views. The IE model proposes that introns are extremely old numerously present in the earliest ancestors of prokaryotes and eukaryotes. In this model introns were lost from prokaryotic organisms. A central prediction of this theory is that the early introns were mediators that facilitated the recombination of exons that represented the protein domains. Such a model would directly lead to the evolution of new genes. The IL model proposes that introns were more recently inserted into original intron-less contiguous genes after the divergence of eukaryotes and prokaryotes. This model is based on the observation that the spliceosomal introns are restricted to eukaryotes alone. However, there is considerable debate on the presence of introns in the early prokaryote-eukaryote ancestors and the subsequent intron loss-gain during eukaryotic evolution. It is also suggested that the evolution of introns and more generally the intron-exon structure is largely independent of the coding-sequence evolution. [1]

Identification

Nearly all eukaryotic nuclear introns begin with GU and end with AG (the GU-AG rule). This mainly occurs in plants.

See also

Structure:

• splice site
• Twintron

Splicing:

• alternate splicing
• Minor spliceosome

Others:

• Eukaryotic chromosome fine structure
• Intein
• Noncoding DNA
• Selfish DNA

References

• Walter Gilbert (1978). "Why genes in pieces". Nature 271 (5645): 501.
• Scott William Roy and Walter Gilbert (2006). "The evolution of spliceosomal introns: patterns, puzzles and progress". Nature Reviews Genetics 7: 211.

External links

• Intron finding tool for plant genomic sequences