Signals for pre‐mRNA cleavage and polyadenylation

Abstract

Pre-mRNA cleavage and polyadenylation is an essential step for 3′ end formation of almost all protein-coding transcripts in eukaryotes. The reaction, involving cleavage of nascent mRNA followed by addition of a polyadenylate or poly(A) tail, is controlled by cis-acting elements in the pre-mRNA surrounding the cleavage site. Experimental and bioinformatic studies in the past three decades have elucidated conserved and divergent elements across eukaryotes, from yeast to human. Here we review histories and current models of these elements in a broad range of species.

U1A Regulates 3′ Processing of the Survival Motor Neuron mRNA

“…Conversely, nothing is currently known about 3Ј processing of the SMN pre-mRNA in the nucleus. In most mRNAs, polyadenylation is signaled by three sequences found in the 3Ј-UTR that interact with the basal polyadenylation machinery: an AAUAAA sequence, a CA dinucleotide at the site of 3Ј cleavage and polyadenylation, and a downstream U-or GU-rich sequence (28). The AAUAAA sequence is bound by the cleavage and polyadenylation specificity factor (CPSF), a four-subunit protein complex that contains the CPSF73 endonuclease (29 -31).…”

A dominant role for meiosis-specific 3′ RNA processing in controlling expression of a fission yeast cyclin gene

“…1D) is very purine-rich, contains only 11 T's and lacks C's entirely; the significance of this unusual base composition is unclear, as the 39 UTR sequences of other mid-meiotic fission yeast genes are ATrich, similar to constitutively expressed genes (data not shown). Although the cleavage site in rem1 follows a GA dinucleotide rather than the consensus YA, a motif related to the conserved hexanucleotide (AATAAA) that serves as a positioning element in metazoan and budding yeast polyadenylation signals (Tian and Graber 2011) is found in a similar location in the rem1 39 UTR (shown in bold type in Fig. 1D).…”

“…The presumptive positioning elements upstream of both cleavage sites in rem1 (Figs. 1D, 6C) also deviate from the consensus hexanucleotide (AAUAAA) (Tian and Graber 2011), whereas the major polyadenylation signal of crs1 contains an exact match to the mammalian consensus (McPheeters et al 2009). Finally, analogous to rem1, testis-specific mouse transcripts often contain deviant hexanucleotides and are inefficiently polyadenylated in somatic cells (McMahon et al 2006;Liu et al 2007).…”

Suppressor of sable [Su(s)] and Wdr82 down-regulate RNA from heat-shock-inducible repetitive elements by a mechanism that involves transcription termination

“…Prior studies have shown that auxiliary pA elements (Millevoi and Vagner 2010;Tian and Graber 2012) can direct efficient CPA in the absence of the AAUAAA motif (Venkataraman et al 2005;Nunes et al 2010). Thus, it is conceivable that several different auxiliary pA elements are responsible for polyadenylation/termination of the unstable αβ RNAs.…”

“…In metazoans, CPA usually depends on the highly conserved consensus element AAUAAA (pA signal), located ∼10-30 nt upstream of the cleavage site (pA site). In addition, U/GU-rich elements, located a short distance downstream from the pA site, and other auxiliary regulatory elements modulate the efficiency of polyadenylation (Millevoi and Vagner 2010;Tian and Graber 2012). During 3 ′ end processing, the CPA machinery cleaves the nascent RNA and adds a long poly(A) tail (∼200 nt in mammals) to the 3 ′ end of the upstream fragment, which becomes the mature mRNA.…”