RNA Processing

The RNA copy of a protein encoding gene must be modified in several ways before it can be transported out of the nucleus and translated into protein. The primary transcription product of a gene is therefore called a precursor of mRNA, pre-mRNA.

Both ends of the pre-mRNA are modified. An additional nucleotide, a 7-methylguanosine is added to the 5'-end to form a cap-structure. This process is called capping (1). The 3'-end of the pre-mRNA is cleaved and polyadenylated (4). The pre-mRNA is cut at a specific site and 150-200 adenylate residues are added to the 3'-end to form a poly(A)-tail. The third major modification is splicing (3). Most, but not all eukaryotic genes contain parts that will be present in the mature mRNA, the exons, and parts that will not be part of the mature mRNA, the introns. The pre-mRNA contains both the exons and the introns and must be cleaved to remove the introns. The exons are at the same time ligated together

splicing »

In addition to the three major processing events, specific nucleotides in some pre-mRNAs can be chemically modified such that the nucleotide sequence is changed. This is referred to as RNA editing.

A considerable number of molecules, both proteins and specialized small nuclear RNAs participate in processing of pre-mRNA. Processing of pre-mRNA is initiated during ongoing transcription and in many instances takes place during transcription. In the cell nucleus, the molecules involved in processing therefore associate with pre-mRNA at actively transcribing genes and may interact with the transcription machinery to coordinate transcription and processing.

Apart from processing factors, pre-mRNA binds to a number of proteins called hnRNP proteins (2). These proteins bind to pre-mRNA immediately as the RNA is made during transcription. There are approximately 30 different types of hnRNP proteins, presumably having different functions. Pre-mRNA is associated with proteins from the time it is made on the gene, during transport (5) through the nucleus to the nuclear membrane pores and into the cytoplasm. It is known that some hnRNP proteins have a role in the nucleus, probably in the transport of the pre-mRNA out of the nucleus. It is also known that hnRNP proteins accompany the mRNA into the cytoplasm, perhaps influencing the fate of the mRNA in the cytoplasm.