9.10
Processamento de pré-mRNA: Modificação das Extremidades do Pré-mRNA
Nas células eucarióticas, as transcrições feitas pela RNA polimerase são modificadas e processadas antes de saírem do núcleo. O RNA não processado é c…
Em células eucarióticas, o mRNA recém-transcrito é chamado de mRNA precursor, ou pré-mRNA. Cada pré-mRNA recebe duas modificações importantes. Um na extremidade de cinco primos da molécula, chamada de tampa, e outro na extremidade de três primos da molécula, chamada de cauda.
A tampa de cinco primos é composta por uma única 7-metilguanosina, um nucleotídeo de guanina modificado, que está ligado ao primeiro nucleotídeo do pré-mRNA por uma ligação trifosfato.
Um conjunto específico de nucleotídeos em direção à extremidade de três primos do transcrito pré-mRNA, geralmente A, A, U, A, A, A, é chamado de sinal de poliadenilação. Ele recruta a maquinaria de processamento de três primos e direciona uma endoribonuclease para cortar o transcrito no local de clivagem de três primos.
Outra enzima, poliadenilato polimerase, ou PAP, adiciona uma longa sequência de nucleotídeos de adenina, até 200, à extremidade de três primos do transcrito.
A tampa de cinco primos e a cauda poli-A de três primos protegem as extremidades do transcrito da degradação por exonucleases. A cauda de três primos também sinaliza para transportar moléculas que o transcrito de mRNA está pronto para deixar o núcleo. Fora do núcleo, a tampa de cinco primos ajuda o ribossomo a se ligar ao transcrito para que ele possa iniciar a tradução.
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Q1: What is the 5' cap and why is it added to pre-mRNA?
The 5' cap is a 7-methylguanosine, a modified guanine nucleotide attached to the first nucleotide of pre-mRNA via a triphosphate linkage. It protects the transcript from degradation by exonucleases and helps the ribosome attach during translation. The cap also helps cells distinguish mRNA from other RNA types.
Q2: How does the poly-A tail protect mRNA and signal its readiness for translation?
Polyadenylate polymerase adds approximately 200 adenine nucleotides to the 3' end of pre-mRNA, forming the poly-A tail. This tail protects mRNA from degradation by exonucleases in the cytoplasm and signals to transport molecules that the transcript is ready to exit the nucleus for translation.
Q3: What is a polyadenylation signal and how does it direct 3' end processing?
A polyadenylation signal is a specific sequence of nucleotides, typically A, A, U, A, A, A, located toward the 3' end of pre-mRNA. It recruits the 3' end processing machinery and directs an endoribonuclease to cut the transcript at the 3' cleavage site, allowing polyadenylate polymerase to add the poly-A tail.
Q4: What is the difference between exons and introns in pre-mRNA?
Exons are RNA sequences that remain in the mature transcript and are expressed as proteins. Introns are portions removed during splicing by the spliceosome. Interestingly, a single RNA segment can function as an exon in one cell type and an intron in another, enabling alternative rna splicing to produce multiple proteins from one gene.
Q5: When does the 5' cap get added during transcription?
The 5' cap is added early during transcription, once approximately 20-40 ribonucleotides have been joined together by RNA polymerase. A group of enzymes replaces the 5' phosphate with modified 7-methyl guanosine, which helps the cell recognize mRNA and prepares it for subsequent translation.
Q6: How do the 5' cap and 3' poly-A tail work together to protect mRNA?
Both the 5' cap and 3' poly-A tail protect mRNA ends from degradation by exonucleases. The 5' cap marks the transcript as mRNA and facilitates ribosome binding, while the 3' tail signals nuclear export and protects the transcript in the cytoplasm, ensuring the mRNA remains stable for translation.
Q7: What happens to pre-mRNA after the 5' cap and poly-A tail are added?
After both modifications are complete, the mature mRNA exits the nucleus for translation. The 5' cap and 3' poly-A tail signal to transport molecules that the transcript is ready to leave the nucleus. Outside the nucleus, the 5' cap helps the ribosome attach to initiate protein synthesis.