The interplay between transcription and mRNA degradation in Saccharomyces cerevisiae

Abstract

The cellular transcriptome is shaped by both the rates of mRNA synthesis in the nucleus and mRNA degradation in the cytoplasm under a specified condition. The last decade witnessed an exciting development in the field of post-transcriptional regulation of gene expression which underscored a strong functional coupling between the transcription and mRNA degradation. The functional integration is principally mediated by a group of specialized promoters and transcription factors that govern the stability of their cognate transcripts by "marking" them with a specific factor termed "coordinator." The "mark" carried by the message is later decoded in the cytoplasm which involves the stimulation of one or more mRNA-decay factors, either directly by the "coordinator" itself or in an indirect manner. Activation of the decay factor(s), in turn, leads to the alteration of the stability of the marked message in a selective fashion. Thus, the integration between mRNA synthesis and decay plays a potentially significant role to shape appropriate gene expression profiles during cell cycle progression, cell division, cellular differentiation and proliferation, stress, immune and inflammatory responses, and may enhance the rate of biological evolution.

Keywords: CLB2; RPL30; Rpb4/7; SWI5; coordinator; functional coupling; mRNA degradation; mRNA mark; promoter; transcription.

Figure 1. FIGURE 1: mRNA life-cycle in eukaryotic cells.

Schematic view of the nuclear and cytoplasmic phases of the mRNA life cycle. Various mRNPs which are recruited onto/associated with the maturing transcripts during different stages are schematically indicated by solid colored symbols. Symbols are either annotated directly or denoted in the associated legend box. THO components/maturing factors/mRNA-binding proteins are released from mRNA once the mRNA matures and becomes export-competent. Similarly, export factors are also released from the transcript body once the mRNA arrives at the cytoplasm and shuttle back into the nucleus. In the cytoplasm, mRNAs may remain associated either with nuclear CBC (while undergoing a pioneer round of translation) or with eIF4E (while undergoing subsequent steady state translation) which is indicated in the diagram. For simplicity, other mRNA binding proteins remaining associated with translating mRNAs are not shown except for CBC and eIF4E. AUG and UAA are indicating the beginning and end of the open reading frame (ORF) carried by the message.

Figure 2. FIGURE 2: Default pathway of mRNA degradation in S. cerevisiae.

Almost all mRNAs undergo decay by the deadenylation-dependent pathway. Thereby, the poly(A) tail is gradually and progressively shortened by the deadenylase activity of the Ccr4/Pop2/Not complex. Following deadenylation, the mRNA can be degraded by one of two mechanisms. The major mechanism involves decapping by Dcp1p/2p, following a 5’→3’ decay by Xrn1p. The minor mechanism includes a 3’→5’ decay by the cytoplasmic exosome and Ski7p. AUG and UAA are indicating the beginning and end of the ORF carried by the message. Only relevant decay components are shown by annotated symbols. Proteins which remain associated to translating/degrading mRNAs during different stages of decay are not shown.

Figure 3. FIGURE 3: The interplay between the transcription and mRNA degradation in S. cerevisiae.

Schematic diagram showing the functional coupling between the mRNA synthesis and degradation. Functional coupling is achieved by marking of the transcribing and maturing messages by various coordinators either through the Rpb1-CTD of RNAPII in a transcription-dependent manner (such as those of Rpb4/7p and Dbf2p) or in a transcription factor (Rap1p)/promoter-dependent manner (such as that of a hitherto unidentified coordinator(s), coded X). The effect of various elements on the recruitment of diverse coordinators is indicated either by the solid (demonstrated) of dashed (postulated) arrow. Export-competent mRNPs undergo translation after arriving in the cytoplasm and are subsequently degraded via the general default decay pathway. During this stage, the Rpb4/7p dependent recruitment of Pat1/Lsm1-7p and influence of Dbf2p together with Dbf20 on the CCR4/NOT complex to further stimulate decay via the activation of other decay components are indicated by the solid arrow. Note that the demonstrated influence of Pat1/Lsm1-7p on the decapping complex is shown by the solid arrow, whereas its potential but questionable impact on CCR4/NOT is indicated by a dashed arrow. Mutual influence of each process on the other is indicated by dashed arrows. Only relevant components are shown by annotated symbols. Other proteins which remain associated to translating/degrading mRNAs (such as eIF4E) during translation and decay are not shown.