Nab2 functions in the metabolism of RNA driven by polymerases II and III

González-Aguilera, Cristina; Tous, Cristina; Babiano, Reyes; Cruz, Jesús de la; Luna, Rosa; Aguilera, Andrés

doi:10.1091/mbc.e11-01-0055

Cited by 32 publications

(43 citation statements)

References 51 publications

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“…In a recent study, we determined the genome-wide occupancy of Nab2 and other nuclear mRNP components in S. cerevisiae by ChIP-chip (Meinel et al 2013). As expected, Nab2 occupies protein-coding genes (Gonzalez- Aguilera et al 2011;Meinel et al 2013). However, we discovered that, in addition to RNAPII transcribed genes, Nab2 also localizes to genes transcribed by RNAPIII.…”

Section: Nab2 Is Recruited To Rnapiii Genesmentioning

confidence: 67%

The poly(A)-binding protein Nab2 functions in RNA polymerase III transcription

2015

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RNA polymerase III (RNAPIII) synthesizes most small RNAs, the most prominent being tRNAs. Although the basic mechanism of RNAPIII transcription is well understood, recent evidence suggests that additional proteins play a role in RNAPIII transcription. Here, we discovered by a genome-wide approach that Nab2, a poly(A)-binding protein important for correct poly(A) tail length and nuclear mRNA export, is present at all RNAPIII transcribed genes. The occupancy of Nab2 at RNAPIII transcribed genes is dependent on transcription. Using a novel temperature-sensitive allele of NAB2, nab2-34, we show that Nab2 is required for the occupancy of RNAPIII and TFIIIB at target genes. Furthermore, Nab2 interacts with RNAPIII, TFIIIB, and RNAPIII transcripts. Importantly, impairment of Nab2 function causes an RNAPIII transcription defect in vivo and in vitro. Taken together, we establish Nab2, an important mRNA biogenesis factor, as a novel player required for RNAPIII transcription by stabilizing TFIIIB and RNAPIII at promoters.[Keywords: RNA polymerase III; Nab2; tRNA; ncRNA; gene expression; TFIIIB] Supplemental material is available for this article. RNA polymerase III (RNAPIII) is responsible for the production of most noncoding RNAs (ncRNAs) such as tRNAs, the 5S rRNA (encoded by RDN5), the RNA of the signal recognition particle (SCR1), the spliceosomal U6 snRNA (SNR6), and the RNA component of RNase P (RPR1). Transcription by RNAPIII is initiated at three classes of promoters, which are highly diverse, have a relatively small number of cis-acting elements, and require comparably few transcription factors (TFs) (White 2011;Orioli et al. 2012;Acker et al. 2013 and references therein). Type 1 promoters are exclusively present at 5S rRNA-encoding genes (RN5S in mammals, and RDN5 in yeast). Type 1 promoters have three internal elements: the A box, which is recognized by TFIIIC, and the intermediate element (IE) and the C box, which are recognized by TFIIIA. The most common RNAPIII promoters are of type 2 and drive transcription of tRNA genes as well as, e.g., the SCR1 and RPR1 genes. Type 2 promoters consist of A-and B-box elements, which together recruit TFIIIC. TFIIIC recruits TFIIIB to the transcription start site at type 1 and type 2 promoters. Type 3 promoters are relatively rare, and, in contrast to type 1 and 2 promoters, all of their elements lie 5 ′ of the transcription start site: the distal sequence element (DSE), the proximal sequence element (PSE), and the TATA box. The DSE recruits the TFs Oct1 and STAF, whereas the PSE recruits SNAP c , which in turn binds TFIIIB and recruits it together with the TATA box to the promoter (Schramm and Hernandez 2002 and references therein). Type 3 promoters are only present in vertebrates; e.g., at the U6 snRNA gene. The promoter of the Saccharomyces cerevisiae U6 snRNA gene SNR6 is of type 2 and contains an upstream TATA box in addition to the canonical A and B boxes (Brow and Guthrie 1990;Eschenlauer et al. 1993). At all three types of promoters, TFIIIB recruits RNAPIII. TFIIIB i...

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Section: Nab2 Is Recruited To Rnapiii Genesmentioning

confidence: 67%

The poly(A)-binding protein Nab2 functions in RNA polymerase III transcription

2015

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“…At present, very little is known about how members of the dNab2/ZC3H14 family of proteins are recruited to nascent transcripts. As mentioned above, a recent study found that yeast Nab2 associates with RNA polymerase II genes in a transcription-dependent manner, 18 and studies in yeast also suggest that Nab2 can interact with the vast majority of poly(A) RNAs. 54 Although most mRNA transcripts should be polyadenylated and therefore theoretically bound by dNab2/ZC3H14, other proteins bound to sequences within the 3' UTR of specific transcripts could also preferentially recruit dNab2/ZC3H14 to specific transcripts.…”

mentioning

confidence: 80%

“…While Pab proteins are typically associated with regulation of mRNAs, there is growing evidence that other types of RNAs also require Pabs for proper regulation. 17,18 The identity of the RNAs or classes of RNAs impacted disability, [13][14][15] is expressed at lower levels in the hippocampus (and specifically the dentate gyrus), perhaps suggesting that disruption of ZC3H14 and FMR1 may impact different cell types in hippocampal circuitry.…”

Section: Members Of a Family Of Znf-containing Pabs Perform Conservedmentioning

confidence: 99%

“…Yeast Nab2 and fly dNab2 both interact genetically with components of the nuclear exosome (our unpublished results and see ref. 18), which is a multiprotein complex required for the proper trimming and quality control of several classes of RNAs transcribed by RNA polymerase III, including rRNAs, tRNAs and small nucleolar RNAs (snoRNAs). [34][35][36] Recent data also suggest that the nuclear exosome may function in the quality control of mRNAs as well.…”

Section: Mutations In the Conserved Znf Pab Zc3h14 Are Linked To Nsmentioning

confidence: 99%

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New kid on the ID block

Kelly¹,

Pak²,

Garshasbi³

et al. 2012

RNA Biology

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Polyadenosine RNA binding proteins (Pabs) play critical roles in regulating the polyadenylation, nuclear export, stability and translation of cellular RNAs. Although most Pabs are ubiquitously expressed and are thought to play general roles in post-transcriptional regulation, mutations in genes encoding these factors have been linked to tissue-specific diseases including muscular dystrophy and now intellectual disability (ID). Our recent work defined this connection to ID, as we showed that mutations in the gene encoding the ubiquitously expressed Cys 3 His tandem zinc-finger (ZnF) Pab, ZC3H14 (Zinc finger protein, CCCH-type, number 14) are associated with non-syndromic autosomal recessive intellectual disability (NS-ARID). This study provided a first link between defects in Pab function and a brain disorder, suggesting that ZC3H14 plays a required role in regulating RNAs in nervous system cells. Here we highlight key questions raised by our study of ZC3H14 and its ortholog in the fruit fly Drosophila melanogaster, dNab2 and comment on future approaches that could provide insights into the cellular and molecular roles of this class of zinc fingercontaining Pabs. We propose a summary model depicting how ZC3H14-type Pabs might play particularly important roles in neuronal RNA metabolism.

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“…Then, initiation factors must be exchanged for elongation factors [15], which are thought to increase the transcription rate and RNAPII processivity. In fact, recently, there has been an extraordinary increase in the number of proteins known to influence transcription elongation by avoiding transcriptional arrest, facilitating chromatin passage and mRNA processing [16][17][18][19][20][21], allowing mRNA packaging into a mature ribonucleoprotein (mRNP) and controlling mRNP quality and mRNA export [13,[22][23][24][25][26][27][28]. Therefore, the discovery of all of these factors has provided further evidence that the elongation phase is also highly regulated in eukaryotic cells and strictly coordinated with other nuclear processes [12][13][14].…”

Section: Introductionmentioning

confidence: 99%