Precursor mRNA

Precursor mRNA (pre-mRNA) is a type of RNA that is an initial transcription product in eukaryotes. It is synthesized from a DNA template in the cell nucleus by RNA polymerase II. Pre-mRNA comprises the bulk of heterogeneous nuclear RNA (hnRNA). Before becoming functional messenger RNA (mRNA) that can be translated into protein, pre-mRNA must undergo several processing steps.

Biogenesis

The synthesis of pre-mRNA begins with the assembly of transcription factors and RNA polymerase II at the promoter region of a gene. The DNA double helix is unwound, and RNA polymerase II transcribes the DNA template into RNA. This RNA transcript includes not only the coding sequences (exon) but also non-coding sequences (intron).

Processing

1. 1. 1. 5' Capping

Immediately after transcription begins, the 5' end of the nascent pre-mRNA is modified by the addition of a guanine nucleotide cap. This cap is important for the subsequent splicing, export to the cytoplasm, and protection from exonuclease degradation.

1. 1. 1. Splicing

Introns are removed from the pre-mRNA through a process called splicing. This is carried out by the spliceosome, a complex of small nuclear ribonucleoproteins (snRNPs). The spliceosome recognizes specific sequence motifs at the intron-exon boundaries and catalyzes the excision of introns, joining the exons together to form a contiguous coding sequence.

1. 1. 1. Polyadenylation

At the 3' end of the pre-mRNA, a sequence of adenine nucleotides called the poly(A) tail is added. This modification is directed by a polyadenylation signal sequence in the pre-mRNA, usually consisting of the hexanucleotide AAUAAA. Polyadenylation is crucial for the stability and export of mRNA from the nucleus.

Function and Significance

The processing of pre-mRNA is a critical step in gene expression. It ensures that the mRNA is mature and ready to be exported from the nucleus to the cytoplasm, where it can be translated into protein. The processes of capping, splicing, and polyadenylation are tightly regulated, and errors in these processes can lead to various genetic disorders and diseases.

Regulation

The regulation of pre-mRNA processing involves numerous proteins and RNA elements that ensure the accuracy and efficiency of mRNA maturation. Regulatory mechanisms include alternative splicing, where the same pre-mRNA is spliced in different ways to produce multiple isoforms of a protein, thus increasing the diversity of the proteome.

See Also

• RNA splicing
• Transcription (genetics)
• Post-transcriptional modification
• Gene expression