The fate of the messenger is pre-determined: a new model for regulation of gene expression

Abstract

Recent years have seen a rise in publications demonstrating coupling between transcription and mRNA decay. This coupling most often accompanies cellular processes that involve transitions in gene expression patterns, for example during mitotic division and cellular differentiation and in response to cellular stress. Transcription can affect the mRNA fate by multiple mechanisms. The most novel finding is the process of co-transcriptional imprinting of mRNAs with proteins, which in turn regulate cytoplasmic mRNA stability. Transcription therefore is not only a catalyst of mRNA synthesis but also provides a platform that enables imprinting, which coordinates between transcription and mRNA decay. Here we present an overview of the literature, which provides the evidence of coupling between transcription and decay, review the mechanisms and regulators by which the two processes are coupled, discuss why such coupling is beneficial and present a new model for regulation of gene expression. This article is part of a Special Issue entitled: RNA Decay mechanisms.

Fig. 1

A. Transcription and decay are coupled processes through imprinting of coordinators onto a nascent mRNA. This imprinting can be mediated via cis or trans factors and it can be promoter or RNAPII dependent (solid lines). There are general coordinators, which are imprinted to a variety of mRNAs (Rpb4/7p, Pab1p (PABPC1), CCR4-NOT, EJC, Dbp5/Rat8p) or class-specific coordinators, which seem to bind to a subset of transcripts (Sus1p, Ssd1p, Dbf2p, αCP, Cth1p, TTP, KSRP, ELAV/Hu, AUF1, TOB/BTG). Transcription and decay can also regulate each other kinetically (dashed lines) to maintain the steady-state levels of cellular mRNAs. B. Alternative TSS and polyadenylation affect 5′ and 3′ UTR lengths. Shorter or longer UTRs allow less or more RBPs to associate with the mRNA and regulate its stability.