The generally expressed hnRNP F is involved in a neural-specific pre-mRNA splicing event.

Min, Hosung; Chan, Raymond C. K.; Black, Douglas L.

doi:10.1101/gad.9.21.2659

Cited by 183 publications

(203 citation statements)

References 52 publications

(59 reference statements)

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“…So far, SR proteins have not been found to bind to these sequences. Although the c-src intronic enhancer binds to a complex of proteins, including the heterogeneous nuclear ribonucleoprotein F (hnRNP F), other proteins that mediate splicing through these regulatory sequences are unknown (Min et al 1995).…”

Section: Scorresponding Author E-mail Dougb@microbiolifesciuclaedmentioning

confidence: 99%

“…This alternative splicing results in a 6-amino-acid insertion within the conserved SH3 domain of Src protein tyrosine kinase. The mouse src N1 exon has proven to be a useful model for understanding both neural-specific splicing and the regulation of short cassette exons in general (Black 1991(Black , 1992Chan and Black 1995;Min et al 1995).…”

Section: Scorresponding Author E-mail Dougb@microbiolifesciuclaedmentioning

confidence: 99%

“…N1 exon inclusion in neurons is under the positive control of an intronic regulatory sequence. The core conserved sequence, called the downstream control sequence (DCS), is between 38 and 70 nucleotides downstream of the N 1 5' splice site (Black 1992;Min et al 1995). In neuronal WERI-1 cell extracts, a complex of proteins assembles specifically onto a DCS RNA (Min et al 1995), and competition experiments indicate that the binding of this DCS complex is required for N1 exon splicing in vitro.…”

Section: Scorresponding Author E-mail Dougb@microbiolifesciuclaedmentioning

confidence: 99%

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A new regulatory protein, KSRP, mediates exon inclusion through an intronic splicing enhancer.

Min

Turck²,

Nikolic³

et al. 1997

Genes Dev.

Self Cite

307

251

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We have purified and cloned a new splicing factor, KSRP. KSRP is a component of a multiprotein complex that binds specifically to an intronic splicing enhancer element downstream of the neuron-specific c-src N1 exon. This 75-kD protein induces the assembly of five other proteins, including the heterogeneous nuclear ribonucleoprotein F, onto the splicing enhancer. The sequence of the KSRP cDNA indicates that the protein contains four K homology RNA-binding domains and an unusual carboxy-terminal domain. KSRP is similar to two proteins, FUSE-binding protein and P-element somatic inhibitor. KSRP is expressed in both neural and non-neural cell lines, although it is present at higher levels in neural cells. Antibodies specific for KSRP inhibit the splicing of the N1 exon in vitro. Moreover, this inhibition of N1 splicing can be rescued by the addition of purified KSRP. KSRP is likely to regulate splicing from a number of intronic splicing enhancer sequences.[Key Words: Alternative splicing; regulatory protein; KSRP; intronic splicing enhancer; RNA-binding protein]

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Section: Scorresponding Author E-mail Dougb@microbiolifesciuclaedmentioning

confidence: 99%

Section: Scorresponding Author E-mail Dougb@microbiolifesciuclaedmentioning

confidence: 99%

Section: Scorresponding Author E-mail Dougb@microbiolifesciuclaedmentioning

confidence: 99%

See 1 more Smart Citation

A new regulatory protein, KSRP, mediates exon inclusion through an intronic splicing enhancer.

Min

Turck²,

Nikolic³

et al. 1997

Genes Dev.

Self Cite

307

251

View full text Add to dashboard Cite

show abstract

“…Some of the trans-acting factors that bind to these G-tracts belong to the heterogeneous nuclear ribonucleoprotein (hnRNP) F/H family of proteins that consists of five members (hnRNP F, hnRNP H, hnRNP H', hnRNP 2H9, and GRich Sequence Factor (GRSF) 1) 9,10 . GRSF-1 is mainly involved in translation regulation 11,12 and Internal Ribosome Entry Site (IRES) mediated translation 13 , while hnRNP H, H' and F are mostly involved in the regulation of alternative splicing [14][15][16][17][18][19][20][21][22][23] and polyadenylation [24][25][26] . The posttranscriptional regulation by hnRNP F/H proteins is a crucial event since mutations in G-tracts often result in aberrant splicing patterns and can be associated with various diseases [27][28][29][30][31][32] .…”

Section: Introductionmentioning

confidence: 99%

Structural basis of G-tract recognition and encaging by hnRNP F quasi-RRMs

Dominguez

Fisette

Chabot

et al. 2010

Nat Struct Mol Biol

132

169

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The heterogeneous nuclear ribonucleoprotein (hnRNP) F is involved in the regulation of mRNA metabolism by specifically recognizing G-tract RNA sequences. We have determined the solution structures of the three quasi RNA recognition motifs (qRRMs) of hnRNP F in complex with G-tract RNA. These structures show that qRRMs bind RNA in a very unusual manner, the G-tract being "encaged", making the qRRM a novel RNA binding domain. We defined a consensus signature sequence for qRRMs and identified other human qRRM-containing proteins, which also specifically recognize G-tract RNAs. Our structures explain how qRRMs can sequester G-tracts maintaining them in a single-stranded conformation. We also show that isolated qRRMs of hnRNP F are sufficient to regulate the alternative splicing of the Bcl-x premRNA strongly suggesting that hnRNP F would act by remodeling RNA secondary and tertiary structures.3

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“…In vitro systems have been highly successful in providing clues to general mechanistic aspects of gene expression (16). Regulated aspects of gene expression at the posttranscriptional level, on the other hand, have been difficult to reproduce in cell-free systems, and limited success has been attained in only a few instances (23,24). In spite of this, much of the effort to develop valid in vitro systems designed to study mRNA stability has focused on mimicking regulated aspects of differential mRNA turnover (reviewed in reference 29).…”

mentioning

confidence: 99%

The Poly(A) Tail Inhibits the Assembly of a 3′-to-5′ Exonuclease in an In Vitro RNA Stability System

Ford

Bagga

Wilusz

1997

Molecular and Cellular Biology

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We have developed an in vitro system which faithfully reproduces several aspects of general mRNA stability. Poly(A) ؊ RNAs were rapidly and efficiently degraded in this system with no detectable intermediates by a highly processive 3 -to-5 exonuclease activity. The addition of a poly(A) tail of at least 30 bases, or a 3 histone stem-loop element, specifically stabilized these transcripts. Stabilization by poly(A) required the interaction of proteins with the poly(A) tail but did not apparently require a 3 OH or interaction with the 5 cap structure. Finally, movement of the poly(A) tract internal to the 3 end caused a loss of its ability to stabilize transcripts incubated in the system but did not affect its ability to interact with poly(A) binding proteins. The requirement for the poly(A) tail to be proximal to the 3 end indicates that it mediates RNA stability by blocking the assembly, but not the action, of an exonuclease involved in RNA degradation in vitro.The relative stability of RNA transcripts plays a key role in determining their steady-state levels as well as the rate of mRNA induction following a transcriptional stimulus (30). Mutations which affect transcript stability can have a very significant impact on regulated gene expression (26,33). The mechanism of regulated turnover of mammalian mRNA, however, is largely unknown. Terminal structures, namely, the 5Ј cap and 3Ј poly(A) tail, serve as general stabilizing elements found on most mRNAs (7,14). Several internal sequences, such as an AU-rich element (10) or nonsense codons (5), which functionally shorten the half-lives (t 1/2 ) of mRNAs have been identified. Furthermore, an internal element which stabilizes ␣ globin mRNA has recently been identified (38). Elucidating how the general and regulatory elements interact to determine the functional t 1/2 of mRNAs is vital to understanding the mechanism of RNA stability as a regulator of gene expression.The poly(A) tail, a posttranscriptional modification of the 3Ј end of all nonhistone mRNAs, is initially formed as a 150-to 200-base homopolymer (19) which assembles multiple molecules of a poly(A) binding protein (PABP) (13). The tail is a dynamic structure which serves as a mediator through which several important cellular processes including the initiation of translation (31), nucleocytoplasmic transport (18), and mRNA stability (7), are regulated. Most mRNAs are rapidly degraded following deadenylation of their 3Ј ends to approximately 30 adenylate residues (8,21,27,34). Many destabilizing elements appear to act by increasing the rate of deadenylation (11). The disruption of poly(A) tail function, therefore, appears to be the rate-limiting step in mRNA turnover. Following deadenylation, mRNA degradation can occur through a variety of exoand/or endonucleolytic pathways (4). The difficulty in identifying intermediates in mammalian mRNA turnover has significantly hindered attempts to probe further into mechanistic aspects of the turnover process.Mechanistic questions in mammalian systems are usually best ...

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The generally expressed hnRNP F is involved in a neural-specific pre-mRNA splicing event.

Cited by 183 publications

References 52 publications

A new regulatory protein, KSRP, mediates exon inclusion through an intronic splicing enhancer.

A new regulatory protein, KSRP, mediates exon inclusion through an intronic splicing enhancer.

Structural basis of G-tract recognition and encaging by hnRNP F quasi-RRMs

The Poly(A) Tail Inhibits the Assembly of a 3′-to-5′ Exonuclease in an In Vitro RNA Stability System

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